Prosocial influences on nicotine reinforcement, reward, and neural signaling in rodent models

Social influences are important determinants of drug initiation in humans, particularly during adolescence and early adulthood. My dissertation tested three hypotheses: 1) conditioned and unconditioned nicotine and social rewards elicit unique patterns of neural signaling in the corticolimbic neurocircuitry when presented in combination versus individually; 2) play behavior is not necessary for expression of social reward; and 3) social context enhances nicotine self-administration. To test the first hypothesis, Fos protein was measured in response to social and nicotine reward stimuli given alone or in combination and in response to environmental cues associated with the rewards in a conditioned place preference (CPP) test. Social-conditioned environmental stimuli attenuated Fos expression in the nucleus accumbens core. A social partner elevated Fos expression in the caudate-putamen, medial and central amygdala, and both nucleus accumbens subregions. Nicotine decreased Fos expression in the cingulate cortex, caudate-putamen, and the nucleus accumbens core. Both stimuli combined elevated Fos expression in the basolateral amygdala and ventral tegmental area, suggesting possible overlap in processing both rewards in these regions. I tested the second hypothesis with an apparatus containing compartments separated by a wire mesh barrier that allowed limited physical contact with a rat or object. While 2 pairings with a partner rat (full physical contact) produced robust CPP, additional pairings were needed for CPP with a partner behind a barrier or physical contact with an object (i.e., tennis ball). The results demonstrate that physical contact with a partner rat is not necessary to establish social-reward CPP. I tested the third hypothesis with duplex operant conditioning chambers separated either by a solid or a wire mesh barrier to allow for social interaction during self-administration sessions. Nicotine (0.015 and 0.03 mg/kg, IV) and saline self-administration were assessed in male and female young-adult rats either in the social context or isolation. Initially, a social context facilitated nicotine intake at the low dose in male rats, but suppressed intake in later sessions more strongly in female rats, suggesting that social factors exert strong sex-dependent influences on self-administration. These novel findings highlight the importance of social influences on several nicotine-related behavioral paradigms and associated neurocircuitry.