Master of Science / Department of Psychological Sciences / Mary Cain / Novelty-seeking and sensation-seeking are traits implicated in initial drug experimentation and relapse in human populations. To research the neurobiological substrates that are implicated in novelty/sensation-seeking that predispose an individual to drug use, a rodent model was used. Recently, 50 kHz ultrasonic vocalizations (USV) have been identified as indices of affective state and are evoked by several drugs of abuse, specifically when these drugs of abuse have their pharmacological effects in the mesolimbic dopamine path. Secondly, genetic breeding of high and low vocalizers suggests not only are they different in the calling frequency, but also to drug sensitivity, suggesting ultrasonic vocalizations may be a behavioral marker for individual differences in the mesolimbic dopamine circuit. Two sensation/novelty seeking screens and an ultrasonic vocalization screen were used in rats to predict the locomotor and 50 kHz USV response to a low (.3 mg/kg) and high dose (1.0 mg/kg) of amphetamine. Correlation analysis revealed none of the novelty screens were correlated. Simultaneous regression analyses indicated amphetamine dose-dependently increased locomotor activity acutely and chronically but did not increase 50 kHz USV. The USV assessment predicted USV response to amphetamine acutely and chronically but was not dose dependent. No interactions among any predictors were observed. Previous research has dichotomized the novelty/sensation-seeking trait and found significant differences between high and low novelty responders. The current research provides evidence for maintaining continuous individual difference variables, and suggests each screen measures a different trait implicated in addiction.

Master of Science / Department of Psychology / Mary E. Cain / Rats reared in an enriched condition (EC) with novel stimuli and social contact with cohorts display less sensitization to nicotine than rats reared under impoverished conditions (IC). However, it is currently unknown what effect differential rearing has on nicotine-induced conditioned hyperactivity. The present study determined whether differential rearing affects conditioning to a nicotine-associated context. In addition, this study also examined the effects of mecamylamine, an antagonist to nicotinic acetylcholine receptors, on conditioned hyperactivity and sensitization. This antagonistic drug has been shown to attenuate the locomotor effects of nicotine. In the current study, EC, IC, and social condition (SC) rats were reared from 21 to 51 days of age before training for the acquisition of conditioned hyperactivity and sensitization. Nicotine (0.4 mg/kg) was administered prior to 1-h locomotor sessions. Conditioned hyperactivity testing followed. Rats then received 5 sessions of sensitization training followed by a 16-day drug-free rest period before being tested for sensitization. Mecamylamine (1.0 mg/kg) was administered to rats prior to the conditioned hyperactivity test and sensitization test. Nicotine treatment resulted in sensitization and conditioned hyperactivity in all differential rearing groups. EC rats displayed less locomotor activity in response to nicotine than both IC and SC rats. Pretreatment with mecamylamine blocked the expression of conditioned hyperactivity in EC and SC rats and attenuated sensitization in all three rearing groups. These findings suggest that environmental enrichment may alter nAChR binding during development and may be a protective factor in the initiation and relapse of smoking behavior.

Doctor of Philosophy / Department of Psychology / Stephen W. Kiefer / Methamphetamine is a potent psychomotor stimulant and a major drug of abuse. There is currently no effective medication available for treatment for methamphetamine addiction. The present study investigated the role of the dopamine D3 receptor on IV methamphetamine self-administration and its effect on methamphetamine induced neurochemical changes. Acute administration of the putative D3 receptor antagonists PG-01037 (10, 30 mg/kg, ip) and SB-277011A (12, 24, mg/kg, ip) significantly decreased the break-point for methamphetamine self-administration under a progressive-ratio (PR) schedule by 45 - 70%. Furthermore, both drugs dose dependently attenuated methamphetamine -triggered reinstatement of drug-seeking behavior in the reinstatement model of relapse. As with other drugs of abuse, the rewarding effects of methamphetamine are believed to be mediated by elevated levels of extracellular dopamine in the mesocorticolimbic system. The present study utilized in vivo microdialysis to examine the neurochemical mechanisms modulating the rewarding effects of methamphetamine actions evident in the various animal models of addiction. In the nucleus accumbens and ventral pallidum, acute methamphetamine (1.0 mg/kg, i.p.,) increased extracellular dopamine by 800 - 900% and decreased GABA by 60 – 65 % in the nucleus accumbens and ventral pallidum. Pretreatment with SB-277011A (12, 24 mg/kg) potentiated the methamphetamine induced dopamine increase but attenuated the methamphetamine-induced GABA decrease. Take together these data suggest that D3 selective antagonists’ pharmacotherapeutic potential in the treatment of methamphetamine addiction may involve a GABAergic mechanism.

Doctor of Philosophy / Department of Psychology / Mary E. Cain / Glutamate contributes to the neurological and behavioral changes that occur during differential rearing, and those that occur during conditioned hyperactivity and sensitization. Metabotropic glutamate receptor 5 (mGluR5) in particular contributes to the psychostimulant reward pathway, plasticity, and differential rearing. The present study examined the role of mGluR5 in conditioning and sensitization in differentially reared rats. Rats were reared in an enriched (EC), impoverished (IC), or social (SC) condition for 30 days, after which they received repeated amphetamine (0.3 mg/kg) or saline injections. Following training, rats received an injection of the mGluR5 antagonist MTEP or saline prior to undergoing conditioned hyperactivity and sensitization tests. Results showed that MTEP attenuated conditioned hyperactivity and sensitization in IC but not EC and SC rats, suggesting that glutamatergic changes occur during differential rearing that alter the effects of MTEP on amphetamine conditioning and sensitization. Additionally, results demonstrated that enrichment rearing has a protective effect against conditioned hyperactivity at low doses of amphetamine.

Master of Science / Department of Psychology / Mary E. Cain / Previous research has shown that both the environment and psychostimulant use influence dopamine levels via the mesolimbic dopamine pathway. C-fos expression has also been observed following exposure to novel environments and psychostimulants. The present study looked to determine the effects of acute amphetamine exposure on locomotor activity and c-fos expression in the basolateral and central nucleus of the amygdala, for rats raised in either an enriched condition (EC), impoverished condition (IC), or social condition (SC). Rats were reared in either the EC, IC, or SC for 30 days, after which they received an acute amphetamine injection (1.0 mg/kg) and locomotor activity was measured. Following the locomotor test rats were perfused and immunohistochemistry was used to measure c-fos levels in the basolateral and central nucleus of the amygdala. Results showed that EC amphetamine rats had significantly greater locomotor activity compared to EC saline rats. There were no significant group or treatment differences in c-fos expression in the ACe. In the BLA SC amphetamine rats had significantly greater c-fos expression than EC amphetamine rats. Overall, the current study revealed that environmental enrichment and amphetamine do significantly alter locomotor activity and c-fos expression in the BLA.

Master of Science / Department of Psychological Sciences / Mary Cain / Research has demonstrated that an enriched rearing environment improves learning in many tasks. However, growing evidence suggests that an enriched environment may not provide the same benefits during a fear conditioning paradigm. In fact, it appears that an isolated rearing environment may facilitate acquisition of fear to an aversive stimulus. The neural mechanisms responsible for this disparity in fear learning among differentially reared animals are currently unknown. The NR2B subunit of the NMDA receptor has been shown to be involved in the acquisition of fear and influenced by differential rearing, making it a prime candidate to begin investigating these underlying neural mechanisms. Therefore, this study assessed the expression of the NR2B subunit in brain regions important for the acquisition of fear (amygdala and hippocampus) among differentially reared rats. Rats were reared in an enriched, an isolated, or a standard condition for 30 days. They received four tone-footshock pairings, after which their brains were removed and expression of the NR2B subunit was quantified in the basolateral amygdala (BLA), central nucleus of the amygdala (ACe), and the CA3 region of the hippocampus. Analyses found that the isolated rats began to acquire fear to the aversive stimulus faster than the enriched and standard housed rats. However, the isolated rats showed the least amount of NR2B expression in the BLA while there were no rearing differences in expression within the ACe or the CA3. The results from this study provide further insight to the importance of the rearing environment in learning and memory, especially the learning of fear, and its central neural basis.

Master of Science / Department of Psychological Sciences / Mary Cain / Individuals suffering from depression primarily rely on pharmacological interventions to alleviate the incapacitating symptoms of the disorder. In addition to genetic differences underlying the etiology of depression, environmental factors play a key role as well. For example, environmental enrichment results in various neurotransmitter alterations, significantly affecting serotonin. To test the efficacy of novel antidepressant drugs in the preclinical laboratory setting, researchers commonly implement the forced swim test (FST) for rats or mice. However, the effect of environmental enrichment on the expression of depressive-like states in the FST is unclear, and it is unknown whether environmental enrichment or social isolation can alter the efficacy of the commonly prescribed antidepressant drug, fluoxetine. In the present study, locomotor activity and FST performance were measured after 30 days of rearing in enriched (EC), standard (SC), and isolated (IC) conditions. Results showed that regardless of the significant effect of fluoxetine on locomotor activity in EC, SC, and IC rats, fluoxetine failed to increase swimming and decrease immobility in all three environmental conditions, with enriched-fluoxetine rats displaying significantly less swimming behavior in the FST than enriched rats receiving vehicle control injections. These results suggest that differential rearing, specifically environmental enrichment, can alter the efficacy of antidepressants and may suggest that enrichment reverses the effects of fluoxetine.

Doctor of Philosophy / Department of Psychological Sciences / Jerome Frieman / Spotted hyenas (Crocuta crocuta) live in highly-complex, female-dominated groups called “clans.” Due to their social arrangement, spotted hyenas were a logical species on which to test the social complexity hypothesis. In the present study, they were presented with a series of puzzle boxes designed to test problem-solving behavior. The five puzzles varied in difficulty. All spotted hyenas solved the puzzle with the lowest difficulty level, five out of six solved the medium puzzles at least once, and one out of six solved the high difficulty puzzle. Some decreases in behavior diversity and time working on the puzzles were observed over successful trials; however, the decreases were only significant for successful trials of one medium-level puzzle. Decreases in work time were observed for some unsuccessful trials and the decrease was statistically significant for the highest difficulty puzzle. Overall, spotted hyenas were proficient at problem solving in the present study. Social learning is an important component of a lengthy juvenile period for spotted hyenas, and they have also been shown to influence one another’s feeding behavior. Furthermore, spotted hyenas participate in scramble competition when feeding and forage for and hoard food. In light of these behaviors, social learning was examined using the social transmission of a flavor preference (STFP) procedure. STFP was not observed overall. The sex of the subjects did not significantly influence the results; however, subjects that interacted with each other longer were significantly more likely to show STFP. The STFP procedure may not be sensitive enough to detect social learning in spotted hyenas. Perhaps spotted hyenas have no need to learn STFP due to their digestive and/or immune systems. The results of the current experiments make important contributions to existing knowledge. Data from other species like spotted hyenas are vital for evaluating the generality of the social complexity hypothesis since support thus far has come from data on primates. This study was the first to investigate STFP in a species from the Feliformia suborder. Additionally, finding more evidence that spotted hyenas have advanced cognitive abilities is essential for researchers and zoo personnel who work with spotted hyenas in captivity.

Doctor of Philosophy / Department of Psychology / Stephen W. Kiefer / Exposing rats to differential rearing conditions, during early post-weaning development, has been shown to produce changes in a number of behaviors displayed during adulthood. The purpose of the current study was to investigate whether rearing alcohol-preferring (P) and non-preferring (NP) rats in an environmental enrichment condition (EC), a social condition (SC), or an impoverished condition (IC) would differentially affect the consumption of and operant responding for 10% ethanol. In Experiment 1 rats were tested for both limited access and free access (two bottle choice between water and ethanol) consumption of 10% ethanol. For, Experiment 2 rats were trained to respond in an operant chamber for ethanol and then provided concurrent access to 10% ethanol (right lever) and water (left lever). After concurrent access, rats were required to respond over a gradually increasing fixed-ratio schedule for 10% ethanol and finally a progressive ratio schedule for 10% ethanol, 15% ethanol, and 10% sucrose. For Experiment 3 rats were trained to respond for 10% sucrose and then assessed for the maintenance of operant responding for 10% sucrose. The data from this series of experiments shows that EC P rats consumed, responded for, and preferred 10% ethanol significantly less than their IC P counterparts. Also, EC P rats did not significantly differ from NP rats during any aspect of testing for all experiments. Experiment 3 failed to reveal a significant effect of rearing although there was a line effect that has been previously observed in the literature. Thus, it would appear from these results that rearing in an EC condition acts to protect alcohol-preferring rats from increased levels of consumption of, preference for, and responding for ethanol compared to rearing in an impoverished environment.

Master of Science / Department of Family Studies and Human Services / Anthony Jurich / This study explored the parents’ perspective of having a child with Autism living in the home. Specifically, the researcher was looking to explore the attachment style between the parent and child, as well as the process of the parents’ changing their expectations of their child, from the expectation of raising a normal child to raising a child with Autism. In order to understand the experience of both families interviewed, the researcher, through semi-structured, qualitative interviews, interviewed each parent separately. A multiple case study approach was used in order to allow for comparison within each family. Methods for analyzing the data included coding the data, so that the data could be analyzed from the individual interviews and also analyzed based on family response. For the parents interviewed in the study, four themes emerged that were similar for all parents. These themes included the diagnosis process, the differences in attachment before and after their child was diagnosed, the changing expectations of themselves, each other and their diagnosed child, and the parents’ views on getting professional help, such as therapy. Both families shared the experience of confusion during the diagnostic process, especially confusion surrounding the cause and prognosis of Autism. All parents in the study illustrated the attachment injury after their child’s diagnosis, in addition to when the child began showing the classic signs of Autism. The study also found that each parent’s expectations changed from higher ones of themselves, spouse and diagnosed child to more moderate and low expectations of their spouse and diagnosed child. Last, all parents interviewed expressed that seeking therapy would have helped them deal with the diagnostic process and better cope with having a child with Autism. It is believed by the researcher that these themes have emerged because of the families’ shared experience of raising an Autistic child.