Methcathinone (MCAT) is the β-ketone analog of methamphetamine, and like its amphetamine analog, MCAT functions as a monoamine releaser that selectively promotes the release of dopamine (DA) and norepinephrine (NE) over serotonin (5-HT). MCAT produces amphetamine-like psychostimulant effects and is classified as a Schedule I drug of abuse by the United States Drug Enforcement Administration (DEA). Recently, synthetic MCAT analogs have emerged as designer drugs of abuse in Europe and the United States and have been marketed under deceptively benign names like “bath salts” in an attempt to evade legal restriction. These dangerous, recently emergent and novel drugs of abuse display varying selectivity to promote release of DA/NE vs. 5-HT, and selectivity for DA neurotransmission is believed to correlate with abuse liability. The goal of this dissertation was to conduct preclinical research to examine structural determinants of abuse-related behavioral and neurochemical effects produced by a series of synthetic MCAT analogs. Specifically, this project focused on one feature of the methcathinone scaffold: the para substituent of the benzene ring. A series of six novel MCAT analogs will be examined to evaluate how physicochemical parameters (steric, Es; electronic, σp; lipophilic, πp) of the para substituent influence in vitro monoamine transporter selectivity as well as in vivo neurochemical and behavioral effects. Results from this body of work implicate steric factors as being particularly important in determining a compound’s abuse-related neurochemical and behavioral effects. Thus, these data not only offer an improved understanding of the mechanism of abuse-related drug effects produced by synthetic MCAT analogs, but also help in the generation of homology models of the human DA and 5-HT transporters (DAT and SERT, respectively).

Hepatitis C is the most common chronic blood-borne infection in the United States. Research has focused on contributing factors to the development and progression of liver disease, but few studies have considered nicotine use as a potential prognostic factor with CHC. Research has commonly found that CHC patients report with a diminished quality of life. Several factors have been proposed to account for a decrease in QOL; however, the mechanisms underlying the impairment in QOL have not yet been elicited. 76 CHC patients completed self-report measures on a variety of psychosocial variables and biochemical data for determining the patient's liver disease severity was obtained. The findings revealed strong support for the deleterious effects of smoking cigarettes on liver disease symptomatology and its progression. Smokers endorsed experiencing significantly more severe symptoms of fatigue, poor appetite, and headaches. The CHC smokers tended to present with higher scores on the Aspartate Arninotransferase to platelet ratio index (APRI). The smokers' mean score is above the cut-off value of 1.50 that indicates a .88 predictive value for the presence of hepatic fibrosis. The level of cigarette consumption could also be a factor in the progression of liver disease. Individuals smoking more than one pack per day tended to report more severe symptoms of fatigue and a poorer appetite. Heavy smokers presented with an APRI mean score above the cut-off value of 2.00 that indicates a .93 negative predictive value for the presence of cirrhosis below the cut-off value.General active coping moderated the relationship between liver disease severity and QOL. The results revealed that patients using more avoidant coping reported lower levels of QOL on the physical and mental component of the SF-36. Tobacco use moderated the relationship between liver disease severity and QOL. Interestingly, smokers reported a higher level of QOL compared to nonsmokers when experiencing more severe liver disease. CHC patients with higher levels of psychological distress reported lower QOL on both physical and mental functioning. Individuals smoking marijuana also tended to report lower levels of QOL on mental functioning. Information garnered from this study is aimed to help slow the progression of advanced liver disease in CHC patients in addition to improving their QOL.

M.Ed. / Drug abuse in secondary schools appears to be a major problem. Preliminary discussions with some learners and educators triggered the researcher to attempt making a research on this matter, since enormities of this problem has a negative impact towards the process of teaching and learning. This type of practice affects the behavioural pattern of individuals within educational institutions. For example learners bring their parents’ revolvers to school to harm their classmates, in class they laugh continuously with no apparent reason, they remain behind with their school work, dress indecently, become arrogant, use vulgar language, rape girls, become disorderly, provoke other learners and start unnecessary fights. The purpose of this study was to explore and investigate whether principals, educators, parents have the necessary knowledge and skills on how to detect the learner as being a drug abuser, how intervention takes place. Further, the research study also tries to determine whether the personnel and Learner Representative Council do check on the food that the vendors are selling to ascertain whether they don’t contain any harmful substances, that can cause a barrier in the learner’s mentality, of which at the end can encourage the learner to turn to crime as a means to survival. Data was collected through a number of methods. Various community members of educational institutions like, principals parents, educators learners and the Gauteng Department of Educators official member, dealing with drugs were interviewed to inquire about their perceptions, feelings and opinions as far as it concerned about intervention strategies for drug abuse in secondary schools. What they recommend should be done to facilitate change on causes of abusing drugs by learners, which strategies to be employed to curb this problem within secondary schools. A thorough literature review was made to determine what other researchers discovered on the same phenomena. Feelings, perceptions and opinions were read throughout the interviews. The participants proved to have a minimal knowledge about the practices of drugs within their schools and the society. By means of particular programmes designed by the school and the society, they can be empowered to open up, in order to provide assistance to the troubled children. / Prof. J.R. Debeila

This study was aimed at the development of novel CB1 cannabinoid receptor antago­nists that may have clinical applications for the treatment of cannabinoid and psychostimulant addiction. The rationale for the design for our target was to incorporate a bioisosteric 1,2,3-triazole ring into the vicinal diaryl group revealed in the prototypical antagonist/inverse agonist SR141716 (Rimonabant) that was pre­sumed to interact with a unique region in the CB1 receptors. Based on our prelimi­nary results we identified a novel series of 1,2,3-triazole ester and keto deriva­tives as lead compounds for biological evaluation. Here in the design rationale, syn­thesis and CB1 receptor affinity for a series of 4,5-diaryl-1-substituted-1,2,3-triazoles of ester and ketones is described. These derivatives were synthesized via a one-pot regiospecific click/acylation reaction sequence from 1-azido-2,4-dichlorobenzene and commercially available arylacetylenes. From the structure-activity studies the 5-(4-chlorophenyl) congeners exhibited the most potent CB1 receptor affinities relative to other 5-(substituted-phenyl) moieties. The 1-(2,4-dichlorophenyl)-5-(4-chlorophenyl)-4-propylcarbonyl-1,2,3-triazole (­31a) was found to be the most potent (Ki = 4.6 nM) CB1 receptor ligand of the series and exhibited high CB1 selectivity (CB2/CB1 = 417). The triazole ester 31a was further characterized as a cannabinoid antagonist in locomotor-activity studies by blocking the locomotor-reducing effects of cannabinoid agonist WIN55,212-2. In addition, unlike the prototypical cannabinoid antagonist SR141716A (Rimonabant), the triazole ester 31a did not exhibit increased activity in locomotor activ­ity studies, thus indicating the potential for a neutral antagonist profile.

Magister Artium (Social Work) - MA(SW) / Heroin usage is on the increase in the Western Cape province of South Africa owing to globalization and to increased access to the drug in this province. The goal of this study is to explore the experiences of coloured heroin users in the Metro South area of , which stretches from Simons Town and Muizenberg to Retreat, Lavender Hill, Grassy Park, Parkwood and Wynberg. These individuals have been found to congregate in the Wynberg CBD. The overarching theoretical framework for the purpose of this research is social constructionism and symbolic interactionism, using a qualitative means of inquiry. Snowball sampling was used to recruit prospective participants and data was collected by means of in-depth interviews, with a semi structures interviewing schedule. The questions informed the subsequent themes and categories that arise from the data collection process. Snowball sampling was employed in this case, a non-probability sample, in which participants were recruited via key informants. The sample distribution included 13 participants, 10 of which were heroin users (5 female, 5 male) and the remaining 3 were key informants which contributed to triangulation of the data. In terms of the findings, participants spoke of mostly being involved in intimate relationships, which according to participants had dual benefits. For female participants intimate relationships offered a form of protection on the often dangerous streets of Wynberg and for certain males, intimate relationships offered an opportunity to fund their habit, by trading their female partners to perform sexual favors for money to acquire heroin. While the study found females were mainly involved in trading sexual favors for money, heterosexual males were also implicated in having sexual relations with homosexual men for money. Furthermore, the study found that heroin users in Wynberg represented a surrogate family, where, because of their lifestyle, they were disconnected from their own family. This family surrogate was found to be supportive, caring to a large extent, shared a living space, protective of each other and shared a common language and understanding.

Title: Criminal legislation of drug abuse Author: Mgr. Markéta Tukinská Supervisor: Prof. JUDr. Jiří Jelínek, CSc. Abstract: Drug abuse is a worldwide problem. The production and illegal trade of drugs is the domain of international organized crime. Illegal weapon trade and human trafficking often follow these activities. The drug abuse means serious threat for the society. It doesn't mean danger only for the drug addict, who is suffering from health problems, which are following the addiction, family and friends alienation, financial problems and losing its place in the society, drug addicts often need medical care, they commit crimes to earn money, because they are unable to do it legally, and they are often carrying and spreading lots of infectious diseases. It's not only the people living on the fringe of society who become drug users. Due to the very rapid lifestyle, consumerism, desire for experiences, which are more intense, even managers who want to be more efficient at their work or young people desiring the amusement are becoming drug users. We should not forget the most famous and abused drug - alcohol. The real danger of this drug is in the social tolerance of drinking alcohol and also its abuse, because not to drink is abnormal for our society. It is not so rare to see on the news that the...

O desenvolvimento encefálico representa um período de grande vulnerabilidade. Embora diversos trabalhos mostrem que a exposição ao fumo passivo pode levar ao desenvolvimento de sintomas psicocomportamentais da farmacodependência, ainda não está claro se a exposição à poluição tabagística ambiental (PTA) na fase inicial de formação do SNC pode levar à predisposição ao uso de drogas de abuso na adolescência. Assim, o foco deste estudo foi avaliar se a exposição à PTA no início do período pós-natal (P) contribui para a sensibilização comportamental e efeitos recompensadores ao etanol e à cocaína durante a adolescência. Camundongos machos Swiss-Webster foram expostos do 3º (P3) ao 15º (P15) dia de vida pós-natal, duas vezes por dia, à mistura da fumaça central e lateral de cigarros referência (3R4F). Na adolescência (P34-P45), foram avaliados os efeitos do tratamento repetido de etanol e cocaína (primeiro protocolo) como também o efeito do tratamento agudo com cocaína (segundo protocolo). No primeiro protocolo os animais foram desafiados com cocaína (i.p) ou etanol (i.p), para a avaliação da sensibilização comportamental (P34-P35) (n=6) e da preferência condicionada por lugar (CPP) (P36-P45) (n=6). A quantificação por Western Blotting (n=6) das proteínas marcadoras de plasticidade, como os receptores dopaminérgicos D1R e D2R, c-Fos, FRA1 e Rac1, no estriado e no córtex pré-frontal (CPF) foi realizada imediatamente após o dia do teste da CPP no P45. Já para o segundo protocolo, os animais foram desafiados com cocaína (i.p) para a avaliação da sensibilização comportamental (P34-P35) (n=12), da CPP (n=10) e a quantificação dos mesmos marcadores bioquímicos (n=6) além da dinorfina-A, nas mesmas estruturas encefálicas que no primeiro protocolo. Essas análises foram realizadas duas horas após a expressão da sensibilização comportamental (P36). O primeiro protocolo avaliou a exposição repetida ao etanol e a cocaína na adolescência na predisposição à dependência enquanto o segundo se a exposição aguda a cocaína seria capaz de levar ao mesmo efeito. No primeiro protocolo observamos sensibilização cruzada pela PTA e quanto ao teste da CPP não foi observada diferença estatística nem para o tratamento com etanol, nem para o com cocaína. Nossos resultados indicam que houve efeito estimulatório nos grupos tratados com cocaína no segundo protocolo deste estudo, representado pelo aumento da atividade locomotora após administração da droga. Por outro lado, não observamos sensibilização cruzada pela PTA, a qual foi obtida no primeiro protocolo. Já para o segundo protocolo, foi observado o condicionamento pela cocaína. Com relação à quantificação das proteínas, nosso estudo mostrou diminuição na concentração de receptores DR1 no estriado no grupo exposto à PTA e tratado com etanol em relação ao grupo controle tratado com etanol no primeiro protocolo deste estudo e sugerem que a exposição repetida ao etanol é capaz de induzir alterações nos receptores de dopamina. No segundo protocolo deste estudo observamos aumento de c-Fos no estriado e no CPF no grupo tratado com cocaína em relação ao seu controle e que a exposição aguda à cocaína é capaz de induzir aumento da dinorfina no CPF, enquanto à exposição prévia à PTA previne este aumento. Vale ressaltar que esse trabalho é inovador uma vez que avaliamos a exposição à PTA na infância e se esta poderia levar a sensibilização cruzada com a cocaína e à alterações em vias envolvidas nesse comportamento na adolescência. Em conjunto, nossos resultados sugerem que a exposição à fumaça do cigarro, mesmo gerando baixas concentrações plasmáticas de nicotina e cotinina, foi capaz de produzir alterações na expressão da sensibilização comportamental, na CPP e alterações bioquímicas, tanto no tratamento repetido de etanol e cocaína quanto na vigência da cocaína. / The brain development represents a very vulnerable period. Although multiples studies showed that exposure to secondhand smoke during the early post-natal period induces impairment in cognitive functions and predisposition to substance dependence psychobehavioral symptoms in adolescents, there is no definitive evidences that exposure to the environmental tobacco smoke (ETS) can lead to the use of drugs of abuse. We aimed to evaluate if the exposure to ETS in the early postnatal period (P) can contribute to the behavioral sensitization and rewarding effects of ethanol and cocaine during adolescence. Using reference cigarettes (3R4F), Swiss-Webster male mice were exposed from the 3rd (P3) to 15th (P15) day of age, twice a day, to the mixture of the cigarettes\' sidestream and mainstream. In adolescence (P34-P45), we evaluated the effects of repeated treatment with ethanol or cocaine (first protocol) and also the effect of acute treatment with cocaine (second protocol). On first protocol, animals were then challenged with cocaine or ethanol to evaluate evidence of behavioral sensitization (P34-P35) (n=6) and conditioned place preference (CPP) (P36-P45) (n=6). Based on Western Blotting analysis, we also quantified proteins markers of plasticity immediately after the day of CPP test (P45), in the prefrontal cortex (PFC) and striatum (dopamine receptors D1R and D2R, c-Fos, FRA1 and Rac1). On second protocol, animals were challenged with cocaine to evaluate evidence of behavioral sensitization (P34-P35) (n=12) and CPP (P36-P45) (n=10). Quantification of those markers of plasticity (n=6), plus dynorphin-A was evaluated two hours after the day of behavioral sensitization expression in P36 in PFC and striatum. The first protocol evaluated the repeated exposure to ethanol and cocaine during adolescence in the predisposition to addiction while the second protocol using acute exposure to cocaine would be able to lead to the same effect. In the first protocol we observed cross-sensitization by ETS and for CPP test, no significant difference for the treatment with ethanol and cocaine were observed. Our results indicated a stimulatory effect in animals challenged with cocaine on second protocol, represented by the increase in locomotors activity after drug administration. On the other hand, we found no cross-sensitization by ETS, which was obtained in the first protocol. As for the second protocol, it was possible to observe the conditioning for cocaine. Regarding our Western Blotting assays, we observed that the group exposed to ETS and challenged with ethanol had decreased D1R in the first protocol of this study. These results suggest that repeated exposure to ethanol could induce changes in dopamine receptors. In the second protocol was an increase of c-Fos in the striatum and the PFC compared to control and that acute exposure to cocaine can induce increase of dynoprhin-A while the prior exposure to ETS prevents this increase on PFC. It is noteworthy that this present study is innovative since it evaluated the exposure to ETS in childhood and this could lead to cross-sensitization with cocaine and changes in pathways involved in this behavior in adolescence. Taken together, our results suggest that exposure to ETS, even findings low levels of nicotine and cotinine plasmatic was able to produce changes in the expression of behavioral sensitization in the CPP and biochemical changes in both the repeated treatment of ethanol and cocaine as in the acute treatment of cocaine.

A recaída ao uso de drogas é um dos principais obstáculos para o tratamento do adicto. Um dos modelos animais mais utilizados para estudar a recaída no laboratório é o chamado de cue-induced. Embora esse modelo tenha se mostrado útil para o estudo de processos neurofisiológicos envolvidos na recaída, seu valor para a análise do controle de estímulos ambientais na dependência tem sido limitado por não distinguir a função dos estímulos discriminativos e dos reforçadores condicionados que controlam a reinstalação da resposta que foi reforçada por droga. O principal objetivo do presente estudo foi analisar os controles estabelecidos sobre as respostas de pressão à barra de ratos submetidos ao procedimento cue-induced. Foram realizados três experimentos. No Experimento 1, os animais passaram pelas três fases experimentais que caracterizam esse modelo. Na primeira fase, a resposta de pressão à barra foi treina em dois componentes distintos. Em um deles, as respostas emitidas na presença de um odor de laranja (SD1) tiveram como conseqüência a apresentação de um estímulo luminoso (Sr1) e liberação de uma solução de etanol (grupo ET) ou de sacarose (grupo SAC). Enquanto na outra, pressões à barra na presença de um odor de erva-doce (SD2) tiveram como conseqüência a apresentação um estímulo sonoro (Sr2) e liberação de água. Na segunda fase, foram realizadas sessões de extinção na ausência dos estímulos utilizados no treino. Na terceira fase os estímulos discriminativos e reforçadores condicionados foram reintroduzidos, mas as respostas de pressão à barra não foram reforçadas por etanol, sacarose ou água. Finalizado o procedimento padrão, foram realizados testes adicionais, nos quais cada estímulo utilizado no treino foi apresentado separadamente. O procedimento do Experimento 2 foi similar ao do Experimento 1, porém foram controladas duas variáveis irrelevantes para o modelo, mas associadas com as contingências experimentais: a maravalha da bandeja da caixa experimental e o acionamento do bebedouro. No Experimento 3, foi adicionada sacarose à solução de etanol e a água. Os resultados dos Experimentos 1 e 2 mostraram que Sr1 foi efetivo em reinstalar a resposta de pressão à barra nos testes de reinstalação realizados, enquanto SD1 foi inconsistente em reinstalar essa resposta. A apresentação de SD2 e Sr2 não reinstalou a resposta. Os dados obtidos no Experimento 3 foram inconclusivos quanto ao controle exercido pelos estímulos olfativos, luminosos e sonoros. Os resultados parecem sugerir que o modelo animal cue-induced, tipicamente usado para estabelecer linhas de base de controle discriminativo sobre a auto-administração de drogas, pode não ser adequado para tal finalidade. No entanto, ainda são necessários refinamentos experimentais para a obtenção de resultados mais acurados. / The relapse into drug use is one of the key obstacles for addict treatment. One of the animal models most used for relapse studies in laboratory is the so called cue-induced. Even though this model has been proven to be useful for neurophysiologic processes related to relapse, its value for analyzing environment stimulus control on addiction is considered to be limited because it does not distinguish the function of discriminative stimulus and of conditioned reinforcer which control the reinstatement of the response that was reinforced by the use of drugs. The main objective of this study was to analyze the established controls over the lever pressure responses of rats submitted to the cue-induced procedure. They were subjected to three different experiments. On the first one the animals were exposed to the three different experimental stages that characterize a cue-induced procedure. At the first experimental phase, lever press response was trained over two different components. In one of them, the response to an orange odor (SD1) had as a consequence the appearance of a luminous stimulus (Sr1) and the release of ethanol (ET group) or a sucrose solution (SAC group). While in the other one, lever press in the presence of a anise odor had as a consequence the appearance of a sonorous stimulus accompanied by water release. At the second phase, there were conducted extinction sessions in the lack of the stimuli used on the training phase. And finally, at the third phase, the discriminative stimulus and conditioned reinforcer were reintroduced. Nevertheless, the lever press response was not reinforced by ethanol, sucrose or water. By the time the standard procedure was over, additional tests were run, where each stimuli used on the training phase were presented to the rats separately. The second experiment procedure was similar to the one employed at the first experiment, however two irrelevant variables for the model were controlled for, but these were associated with the experimental contingencies: the sawdust on the experimental box trail and the drinking fountain when put into action. At the third experiment, sucrose was added to the ethanol solution and also to the water. The results from the two first experiments showed that Sr1 was effective in reinstate the lever pressure response verified at the reinstatement tests, whereas SD1 was not successful in doing so. Neither the introduction of SD2 nor Sr2 reinstate the response. The data obtained by Experiment 3 was not conclusive in regards to the control imposed by the olfactory, luminous and sonorous stimuli. The results suggest that the cue-induced procedure, typically used to establish baselines for discriminative control over drugs self-administration, may not be in fact the most suitable one for this purpose. Nonetheless, there is still a need to refine the experiment in order to reach more accurate and conclusive results.

Esta pesquisa apresenta os dados sobre o uso de drogas legais e ilegais pelos alunos de graduação da USP - campus São Paulo - no ano de 2001 e os compara aos dados obtidos em 1996. 2837 estudantes responderam a um questionário anônimo e de auto-preenchimento que levantou o uso de drogas na vida, nos últimos 12 meses e nos últimos 30 dias. A comparação entre 1996 e 2001, mostrou que houve um aumento significativo de uso de álcool, tabaco, maconha, alucinógenos, anfetaminas, anti-colinérgicos, inalantes, barbitúricos e drogas ilegais. Estes dados reforçam a necessidade do desenvolvimento de atividades de prevenção do abuso e de redução dos danos decorrentes do uso destas substâncias. / This dissertation presents data about drug use behaviors among undergraduate students from USP, Brazil, in 2001 and compares these data with the data obtained in 1996. 2837 students responded an anonymous and self-response questionnaire that obtained information about lifetime, past-12month and past-30day drug use prevalence. The comparison between the two surveys showed that the use of alcohol, tobacco, marijuana, inhalants, hallucinogens, amphetamines, anticolinergics, barbiturates and illegal drugs increased significantly. These data reinforce the need of developing drug use and abuse prevention activities and harm reduction strategies.

O tratamento com morfina ao final da prenhez, faz com que uma única dose dessa droga durante a lactação iniba o comportamento maternal e estimule a caça predatória. A intensidade dessa mudança comportamental depende da dose desafio de morfina utilizada. A exposição a drogas de abuso pode levar a um fenômeno denominado tolerância reversa, que consiste na exacerbação dos efeitos do tratamento agudo com um fármaco observada após a interrupção de um tratamento crônico. O objetivo deste estudo foi avaliar como os efeitos do pré-tratamento com morfina durante a gestação podem influenciar na seleção comportamental após o parto. Ratas foram expostas simultaneamente a filhotes e insetos, sendo observada a expressão dos comportamentos maternal e predatório. As ratas foram tratadas com injeções diárias de morfina (3,5 mg/Kg, s.c.) do 17º ao 21º dia de gestação, e desafiadas agudamente no 5o ou 6o dia de lactação com doses distintas de morfina (0,5, 1,0 e 1,5mg/Kg; grupos MM0,5, MM1,0 e MM1,5) ou salina (grupo MS). Grupos controle foram pré-tratados com salina e desafiados com morfina (0,5, 1,0 e 1,5mg/Kg; grupos SM0,5, SM1,0 e SM1,5) ou salina (grupo SS), respectivamente. Em seguida foram testadas no paradigma de escolha entre cuidar dos filhotes e caçar. Animais pré-tratados com morfina e desafiados com 1,0 mg/Kg tiveram parâmetros de comportamento maternal prejudicados e facilitação ao comportamento de caça de maneira significante, o que não foi observado nos animais desafiados com a dose de 0,5 mg/Kg. Animais desafiados com 1,5 mg/Kg de morfina tiveram prejuízo em relação ao comportamento maternal e facilitação do comportamento predatório tanto no grupo de fêmeas pré-tratadas com morfina, quanto com salina. Em ratas lactantes a exposição simultânea a filhotes e insetos permitiu revelar a existência de tolerância reversa à mudança comportamental induzida por estímulo opioidérgico. / Treatment of postpartum female rats with morphine inhibits maternal behavior. The same treatment also stimulates foraging in adult animals. Exposure to drugs of abuse may result in a progressive and enduring enhancement of their reinforcing effects. Puerperal treatment with morphine leads to reverse tolerance to this drug, ultimately influencing the effects of opiates on maternal behavior. The aim of the present study was to investigate whether abrupt withdrawal from repeated morphine treatment during late pregnancy may influence the effects of morphine on behavioral selection in lactating rats. Animals were exposed simultaneously to pups and insects, and the choice between taking care of the pups and hunting for insects was observed. Female Wistar rats were treated with morphine (3.5 mg/kg/day, subcutaneous [s.c.]) or saline for 5 days beginning on pregnancy day 17. On day 5 of lactation, animals were acutely challenged with morphine (0.5, 1.0, or 1.5 mg/kg, s.c.; MM0.5, MM1.0, and MM1.5 groups, respectively) or saline (MS group) and simultaneously tested for predatory hunting and maternal behavior. Control groups were pretreated with saline and challenged with morphine (SM0.5, SM1.0, and SM1.5 groups) or saline (SS group). Animals treated with morphine during late pregnancy and acutely challenged with 1.0 mg/kg morphine (MM1.0 group) exhibited significantly decreased maternal behavior and enhanced hunting. This effect was not evident for the 0.5 mg/kg dose. The 1.5 mg/kg morphine dose decreased maternal behavior and increased hunting in both the MM1.5 group and in animals acutely challenged with morphine after previous saline treatment (SM1.5 group). These results provide evidence of plasticity of the opioidergic role in behavioral selection during lactation.