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 / 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.

In the USA, approximately 15% of women smoke tobacco cigarettes during pregnancy. In utero tobacco smoke exposure produces somatic growth deficits like intrauterine growth restriction and low birth we

The aim of this investigation was to determine the effect of a nicotine-conditioned context on locomotor hyperactivity in an animal model of D2-priming, and whether conditioned hyperactivity could be blocked by the D2 antagonist eticlopride or the D3 antagonist nafadotride. D2-primed male rats showed enhanced nicotine sensitization as evidenced by statistically significant differences in horizontal activity. D2-primed female rats administered nicotine demonstrated an increased hypoactive response after initial sensitization and increased stereotypy. Eticlopride and nafadotride blocked sensitization to nicotine in both D2-primed and non D2-primed males and females. Eticlopride blocked conditioned hyperactivity in females but not in males. D2-primed female rats administered nicotine demonstrated significantly higher conditioned-hyperactivity as compared to non D2-primed females and controls, and this increase was more effectively blocked by nafadotride as compared to eticlopride. These results suggest differential roles of the dopamine D2 and D3 receptors in both adolescent nicotine sensitization and conditioned activating effects of nicotine.