Previous research has demonstrated that memory is dependent on the environmental context; memory is better when the same environmental context cues present at study are reinstated at test as compared to when they are not. This finding is called context reinstatement effects (Godden & Baddeley, 1975; Smith, Glenberg, and Bjork, 1978; Smith & Vela, 2001). What is unclear is whether study items are associated with the global context or with unique features within the study environment. We tested whether reinstating a singular feature of a global environment, the odor present during study, was sufficient to produce context reinstatement effects. These results indicated that, in a global environmental context, the global context is not being used as a cue for all the studied items rather than unique aspects of the environment serving as unique cues.

It has been proposed that relapse vulnerability in previously dependent individuals results from augmentation of drug-induced reinforcement due to repeated associations between the interoceptive properties of the drug and reduction of acute withdrawal distress. To test this hypothesis, male Sprague-Dawley rats self-administered 0.05 mg/kg/inf heroin on continuous and progressive ratio (PR) schedules. During this period, they also received injections of vehicle or escalating doses of heroin. Following tests of naloxone-precipitated withdrawal (0.01 or 0.1 mg/kg, SC), as well as abstinence (4 days), and extinction training (9 sessions), they were pre-treated with vehicle or yohimbine (0.5 mg/kg, IV) and tested for resumption of heroin self-administration (0.05 mg/kg/inf) on continuous and PR schedules (Experiments 1 & 2), or tested for reinstatement in extinction conditions. Differences between vehicle- and heroin-injected rats were noted on self-administration on the continuous reinforcement schedule, but not on the PR schedule, in spite of greater signs of withdrawal precipitated by naloxone in the heroin-injected rats. More importantly, there were no group differences in resumption of heroin self-administration, and this was not altered by yohimbine. These results suggest that relapse vulnerability cannot be uniquely ascribed to the altered reinforcing action of drugs; contextual and other conditioning factors must play a role in modulating resumption of drug intake after periods abstinence.

Summary Unseeing and weak-eyed women occupational reinstatement: model construction. In the master work there is reaching to highlight a reinstatement procedure’s importance for unseeing and weak-eyed women social integration fortune. There in this work is a new view to occupational reinstatement model do not analyze the model’s constituents but unclosing interaction between separate links importance and model’s influence to seeing disabled women social integration process. According to the problem of the research, subject and object’s phrasing, there is risen an aim of the research – accounting Lithuania’s socio-cultural and socio-educational experience, to identify the luck factor seeing disabled women social integration to the work market and unclosing their content and evaluating the expression. There were realized the following research’s tasks: observed and theoretically reasoned reinstatement of the unseeing and weak-eyed women, there is done a research of seeing disabled women integration into work market, the material has been processed statistically and qualitatively, set and evaluated substantial seeing disabled women integration to the work market factor of the success and given the recommendations how to improve seeing disabled women integration to the work market. The methodological reason is made of various theoretical assumptions in the master work: 1) contemporary professional training (constant individuality education, the whole life learning)... [to full text]

Six separate experiments were conducted to investigate the role of Field Dependency (FDI) in determining the susceptibility of eyewitnesses to context reinstatement (CR); their performance in free, cued, and multi-choice recall, and facial identification accuracy; and finally the confidence expressed before and after performing these tasks, and the confidence accuracy relationship (C/AR). Questions were also addressed in relation to the measurement scale status of confidence ratings and the validity and utility of the Calibration / Resolution techniques for analysing the C/AR. Experiments I & II focussed on FDI and CR susceptibility, together with accuracy in free recall, cued recall, and recognition. Experiments III & IV focused on FDI, CR, and recognition. Experiment IV also utilised the Calibration / Resolution technique. Experiment V used a computer presented format to focus on FDI and recognition through simultaneous and sequential line-ups presented upright and inverted. Experiment VI included multi-choice recall testing along with free and cued recall and focussed on FDI, CR, and both correct and incorrect information produced. Experiments I, II, & VI indicated that Field Dependent (FD) participants benefited significantly from CR whilst Field Independent (FI) participants did not. FIs consistently outperformed FDs in cued recall. Experiment VI indicated that for FDs CR in free recall increased correct information and decreased erroneous information, leading to a significant improvement in the 'quality' of the information produced. In cued recall, however, correct information produced by FIs was greater than that produced by FDs and erroneous information lower, leading to a significant difference between FDs and FIs in the 'quality' of cued recall produced. Experiments III and IV indicated a significant superiority in facial recognition for FDs as compared to FIs across time delays of one week and three months in filled line-ups but not in blank. The explicit encoding format and upright and inverted lineups used in experiment V indicated a role for both attentiveness to others and configural processing in the superiority of FDs seen in experiments HI & IV. Results across experiments I, II, and VI indicated that confidence was significantly higher following a free recall test than when assessed at other points during recall testing. In experiment III, IV, & V confidence ratings were higher following exposure to the line-up than confidence ratings given before exposure. Results across all six experiments in relation to the C/AR show a marked level of inconsistency, however the use of the calibration / resolution techniques in experiment IV indicated a level of over-confidence on the part of FIs and underconfidence on the part of FDs that is in keeping with the personality aspects of FDI. In experiment VI the same techniques in relation to cued recall indicate a degree of overconfidence for 'easy' questions and under-confidence for 'hard' questions and point to a new approach to the investigation of the role of 'item difficulty' in determining the C/AR. Overall, the thesis argues that cognitive style is an important factor in predicting when context reinstatement will be beneficial, who will perform better in different recollection and recognition tasks, and how confidence will relate to accuracy.

There are several lines of evidence supporting the existence of a pivotal role of the cannabinoid system in mediating the reinforcing effects of nicotine. Characterization of the crosstalk between nicotine addiction and the cannabinoid system may have significant implications for our understanding of the neurobiological mechanisms underlying nicotine dependence. Objectives: The current series of experiments, we investigated the effects of activating CB1 receptors, modulating CB2 receptors as well as elevating levels of the endogenous cannabinoid ligand anandamide on nicotine taking and reinstatement of nicotine seeking behaviour. METHODS: In the first series of experiments, we investigated the effects of pretreatment with the CB receptor agonist WIN 55, 212-2 (0.1-1mg/kg), on nicotine self-administration and on the reinstatement of nicotine seeking behaviour. In the next series of experiments, we used a selective CB1 inverse agonist rimonabant (0.3mg/kg) and CB2 antagonist AM630 (5mg/kg) to delineate wether the effects obsereved with WIN 55, 212-2 are CB1 or CB2 meidated. Moreover, we investigated the effect of selective CB2 receptor activation (AM1241 1-10 mg/kg) and inhibition (AM630 1.25-5 mg/kg) on nicotine self-administration under fixed ratio (FR) and progressive (PR) schedules of reinforcement and on reinstatement of nicotine seeking induced by nicotine associated cues and nicotine priming. Finally, the effects of activation of CB receptors through administration of anandamide reuptake inhibitor VDM11 (1-10 mg/kg) on nicotine self-administration and on reinstatement of nicotine seeking were investigated. RESULTS: WIN 55,212-2 enhanced the break points for nicotine self-administration under a PR schedule of reinforcement, reinstated nicotine seeking behaviour and enhanced cue induced reinstatement of nicotine seeking. Neither activation nor blockade of CB2 receptors affected the responding of the animals for nicotine self-administration under FR or PR schedules of reinforcement or for reinstatement of nicotine seeking induced by nicotine associated cues and priming. Pretreatment with VDM11 dose dependently attenuated the reinstatement of nicotine seeking behaviour induced by nicotine associated cues and priming without affecting stable nicotine self administration. CONCLUSION: CB1 but not CB2 receptors appear to play a pivotal role in modulating the reinforcing effects of nicotine. Inhibition of anandamide reuptake could be a potentially useful tool in modulating relapse to smoking

There are several lines of evidence supporting the existence of a pivotal role of the cannabinoid system in mediating the reinforcing effects of nicotine. Characterization of the crosstalk between nicotine addiction and the cannabinoid system may have significant implications for our understanding of the neurobiological mechanisms underlying nicotine dependence. Objectives: The current series of experiments, we investigated the effects of activating CB1 receptors, modulating CB2 receptors as well as elevating levels of the endogenous cannabinoid ligand anandamide on nicotine taking and reinstatement of nicotine seeking behaviour. METHODS: In the first series of experiments, we investigated the effects of pretreatment with the CB receptor agonist WIN 55, 212-2 (0.1-1mg/kg), on nicotine self-administration and on the reinstatement of nicotine seeking behaviour. In the next series of experiments, we used a selective CB1 inverse agonist rimonabant (0.3mg/kg) and CB2 antagonist AM630 (5mg/kg) to delineate wether the effects obsereved with WIN 55, 212-2 are CB1 or CB2 meidated. Moreover, we investigated the effect of selective CB2 receptor activation (AM1241 1-10 mg/kg) and inhibition (AM630 1.25-5 mg/kg) on nicotine self-administration under fixed ratio (FR) and progressive (PR) schedules of reinforcement and on reinstatement of nicotine seeking induced by nicotine associated cues and nicotine priming. Finally, the effects of activation of CB receptors through administration of anandamide reuptake inhibitor VDM11 (1-10 mg/kg) on nicotine self-administration and on reinstatement of nicotine seeking were investigated. RESULTS: WIN 55,212-2 enhanced the break points for nicotine self-administration under a PR schedule of reinforcement, reinstated nicotine seeking behaviour and enhanced cue induced reinstatement of nicotine seeking. Neither activation nor blockade of CB2 receptors affected the responding of the animals for nicotine self-administration under FR or PR schedules of reinforcement or for reinstatement of nicotine seeking induced by nicotine associated cues and priming. Pretreatment with VDM11 dose dependently attenuated the reinstatement of nicotine seeking behaviour induced by nicotine associated cues and priming without affecting stable nicotine self administration. CONCLUSION: CB1 but not CB2 receptors appear to play a pivotal role in modulating the reinforcing effects of nicotine. Inhibition of anandamide reuptake could be a potentially useful tool in modulating relapse to smoking

Rationale: Psychotic disorders such as schizophrenia are often accompanied by high rates of cigarette smoking, reduced quit success, and high relapse rates, negatively affecting patient outcomes. However, the mechanisms underlying altered relapse-like behaviors in individuals diagnosed with psychosis are poorly understood. Objectives: The present study analyzed changes in extinction and reinstatement of nicotine conditioned place preference (CPP) and resulting changes in brain-derived neurotrophic factor (BDNF) in a novel heritable rodent model of psychosis, demonstrating increased dopamine D2 receptor sensitivity, to explore mechanisms contributing to changes in relapse-like behaviors. Methods: Male and female offspring of two neonatal quinpirole-treated (QQ) and two neonatal saline-treated (SS) Sprague-Dawley rats (F1 generation) were tested on an extended CPP paradigm to analyze extinction and nicotine-primed reinstatement. Brain tissue was analyzed 60 min after the last nicotine injection for BDNF response in the ventral tegmental area (VTA), the infralimbic (IfL) and prelimbic (PrL) cortices. Results: F1 generation QQ offspring demonstrated delayed extinction and more robust reinstatement compared to SS control animals. In addition, QQ animals demonstrated an enhanced BDNF response to nicotine in the VTA, IfL and Prl cortices compared to SS offspring. Conclusions: This study is the first to demonstrate altered relapse-like behavior in a heritable rodent model with relevance to comorbid drug abuse and psychosis. This altered pattern of behavior is hypothesized to be related to elevated activity-dependent BDNF in brain areas associated with drug reinforcement during conditioning that persists through the extinction phase, rendering aberrantly salient drug associations resistant to extinction and enhancing relapse vulnerability.

Thesis advisor: Stephen C. Heinrichs / This study investigated the effects of baclofen, a GABAB agonist, on modulating drug seeking and drug reward in a novel model of reinstatement. To investigate drug seeking, rats were trained to nosepoke for cocaine infusions, given a drug holiday, and under a baclofen pretreatment (0, 0.2, 1, or 5 mg/kg i.p.), were exposed to an odor conditioned discriminative stimulus (DS+) that reinstated cocaine self-administration. To investigate drug reward, an odor reactivity test was used. Rats were tested for changes in odor preference after the acquisition, drug holiday, and reinstatement phases of self-administration behavior were each completed. Pretreatment with the low dose of baclofen (0.2) attenuated cocaine seeking primed by a conditioned DS+. Medium doses (1.0) caused no change in drug seeking. High doses (5.0) caused a reduction in drug seeking, but this was due to motor impairment. No doses of baclofen had any affect on the rewarding properties of cocaine or cocaine-associated stimuli. It can be concluded that GABAB receptors have no role in modulating the rewarding properties of drug rewards or drug-associated stimuli, but instead play a role in modulating drug seeking. In rats that were exposed to a drug in the past, low levels of GABAB receptor activation reduce drug-seeking, while medium to high levels could have reduced dopamine levels to the point that increased drug seeking or motor impairment was seen. / Thesis (BA) — Boston College, 2004. / Submitted to: Boston College. College of Arts and Sciences. / Discipline: Psychology. / Discipline: College Honors Program.

The abuse of and addiction to drugs of abuse, such as tobacco, alcohol, opioids, and illicit drugs, are growing global problems that affect the welfare of individuals and societies worldwide. The National Institute of Drug Abuse estimates the annual cost of substance abuse to be over $740 billion in costs related to drug intoxication, withdrawal and relapse. A primary challenge in the treatment of substance abuse is the tendency of users to relapse following acute or extended periods of abstinence; on average over 60% of substance abusers will return to drug use within a year of receiving treatment, many relapsing following stressful life events. Central to the successful treatment of drug addiction is understanding the cellular mechanisms by which relapse episodes occur. Current data suggest that the activation of pituitary adenylate cyclase activating peptide (PACAP) systems in the bed nucleus of the stria terminalis (BNST) is an important event underlying stress-induced reinstatement to drug-seeking in a rodent model of stress-induced relapse. In conjunction with immunohistochemistry and pharmacological treatments, we used this behavioral model of stress-induced relapse to evaluate PACAP and PACAP type-1 receptor (PAC1-R) signaling in stress-induced reinstatement to cocaine seeking. Activation of the PAC1 receptor appears to be critical to stress-induced reinstatement, as the selective PAC1-R agonist, maxadilan, produced reinstatement behaviors in the absence of stress. Moreover, BNST pretreatment with either mitogen activated protein kinase-ERK (MEK) or endocytosis inhibitors to block extracellular signal-related kinase (ERK) signaling attenuated stress-induced reinstatement. Furthermore, BNST phosphorylated ERK (pERK) expression, mediated by PAC1-R activation, is substantially potentiated in cocaine-experienced animals after stressor exposure, in a manner that is dependent on endosomal signaling and MEK activity. These data suggest that the activation of a PAC1 signaling cascade is a key event underlying stress-induced reinstatement. Furthermore, this data may suggest a permanent change in the BNST PACAP system (sensitization) following cocaine exposure.

The prefrontal cortex (PFC) is considered a critical node in the neural circuitry underlying drug-seeking behaviors. However, the mechanisms by which this region influences drug seeking and whether or not the lateral PFC mediates cocaine or heroin seeking are questions that have yet to be answered. To expand on the role of the PFC in drug seeking, rats were trained on either heroin or cocaine self-administration for a minimum of 12 days before undergoing extinction training and subsequent reinstatement tests (cued and drug-prime). All pharmacological manipulations were delivered immediately prior to reinstatement testing and were targeted at either the ventral region of the medial PFC, the infralimbic cortex (IL), the anterior portion of the medial PFC, the medial orbitofrontal cortex (mOFC), the anterior region of the insular cortex, the dorsal agranular insular cortex (AId), or the posterior region of the insular cortex, the posterior insular cortex (PIc). In chapter 1, D1 and D2 antagonists were administered into the IL and mOFC prior to cued and cocaine-prime reinstatement. Although previous studies found that the IL inhibits cocaine seeking, blocking D1 receptor activity in this region reduced cued reinstatement and had no effect on cocaine-prime reinstatement, indicating that the IL can promote cocaine seeking under certain circumstances. In contrast, blocking D1 receptors in the mOFC reduced all forms of reinstatement that were examined. Blocking D2 receptors in either region had no effect on cocaine seeking. Our data are the first to demonstrate a role for the mOFC in cocaine seeking and suggest that although the IL and mOFC lie immediately adjacent to one another, they play distinct roles in mediating cocaine seeking. In chapter 2, we pharmacologically inactivated the AId and PIc via a GABA agonist administered immediately prior to both cocaine and food seeking. Reversible inactivation of the AId reduced cued reinstatement but had no effect on cocaine-prime reinstatement. In contrast, inactivating the PIc had no effect on any form of cocaine seeking. Additionally, blocking the AId during cued and food-prime reinstatement had no effect on food seeking, indicating the role of the AId in reinstatement is specific to cocaine seeking and not general motivated behavior. Additionally, blocking CRF1 receptors in the AId blocked cued reinstatement, suggesting a possible mechanism whereby the AId is influencing cocaine seeking. These data are the first to establish a role for the AId in cocaine seeking and demonstrate that although the PIc influences alcohol and nicotine seeking, it does not mediate cocaine seeking. Chapter 3 further examined the role of the AId in cocaine seeking and expanded the influence of the insular cortex in drug seeking to heroin. AId D1 receptor blockade reduced both cued and cocaine-prime reinstatement following extinction training, whereas D2 receptor blockade had no effect on cocaine seeking. These results establish a role for the AId in cocaine-prime reinstatement, as pharmacological inactivation showed no role for the AId in cocaine-induced drug seeking. Additionally, blocking the AId during heroin seeking potentiated cued reinstatement whereas blocking the PIc during heroin seeking reduced cued reinstatement. These results demonstrate a role for the insular cortex in heroin seeking that has never been shown before and further explain how the AId may be influencing cocaine seeking.