The Impact of Adolescent Alcohol Exposure on Nicotine Behavioral Sensitization in the Adult Male Neonatal Ventral Hippocampal Lesion Rat

Nicotine and alcohol use is highly prevalent among patients with serious mental illness, including those with schizophrenia (SCZ), and this co-occurrence can lead to a worsening of medical and psychiatric morbidity. While the mechanistic drivers of co-occurring SCZ, nicotine use and alcohol use are unknown, emerging evidence suggests that the use of drugs during adolescence may increase the probability of developing psychiatric disorders. The current study used the neonatal ventral hippocampal lesion (NVHL) rat model of SCZ, which has previously been shown to have enhanced nicotine behavioral sensitization and, following adolescent alcohol, increased alcohol consumption. Given how commonly alcohol is used by adolescents that develop SCZ, we used the NVHL rat to determine how exposure to adolescent alcohol impacts the development of nicotine behavioral sensitization in adulthood. Male Sprague-Dawley rats underwent the NVHL surgery or a sham (control) surgery and subsequently, half of each group was allowed to drink alcohol during adolescence. Nicotine behavioral sensitization was assessed in adulthood with rats receiving subcutaneous injections of nicotine (0.5 mg/kg) each day for 3 weeks followed by a nicotine challenge session 2 weeks later. We demonstrate that all groups of rats became sensitized to nicotine and there were no NVHL-specific increases in nicotine behavioral sensitization. We also found that NVHL rats appeared to develop sensitization to the nicotine paired context and that adolescent alcohol exposure blocked this context sensitization. The current findings suggest that exposure to alcohol during adolescence can influence behaviors that manifest in the adult NVHL rat (i.e., context sensitization). Interestingly, nicotine behavioral sensitization levels were not altered in the NVHL groups regardless of adolescent alcohol exposure in contrast to prior reports.

Paradoxical Enhancement of Spatial Learning Induced by Right Hippocampal Lesion in Rats

The left–right hemispheric differences in some brain functions are well known in humans. Among them, savant syndrome has unique features, such as exceptional abilities in vision, memory, computation, and music, despite brain abnormalities. In cases of acquired savant and transient savant, brain damage or inhibition is often seen in the left hemisphere, suggesting a link between left hemispheric dysfunction and these talents. On the other hand, some functional left–right differences have been reported in rodent brains, and therefore, unilateral damage in rodents may also result in savant-like enhancements. In the present study, we examined the effects of hippocampal damage on spatial learning in rats with left, right, or bilateral hippocampal lesion. The results showed that learning performance was impaired in the bilateral lesion group, and there was no significant difference in the left lesion group, while performance was enhanced in the right lesion group. These results suggest that damage to the right hippocampus in rats may lead to savant-like enhancement in learning and memory. The construction of the savant model through these results will contribute to the neuroscientific elucidation of the paradoxical phenomenon observed in savants, that some abilities are enhanced despite their brain dysfunction.