Gender Moderates Chronic Nicotine Cigarette Effects on Verbal Memory in Young Adults.

Background: Rates of nicotine use remain a prominent public health concern, especially among young adults. Previous findings have demonstrated that chronic exposure to nicotine during adolescence may be linked to various neurocognitive deficits. Nicotine differentially affects the brain by gender. Objectives: The present study investigated the effects of gender and chronic nicotine use on cognition in the developing brain. Methods: From 2008 to 2011, 57 young adult (ages 18-25) participants were recruited as part of a larger cross-sectional neuroimaging study and divided into 21 nicotine users (12 female) and 36 non-using controls (17 female). Participants completed various questionnaires, drug use interview, neuropsychological battery, and MRI scan in a university setting. A series of multiple regressions was conducted with nicotine group and gender*nicotine group interaction as predictors. Results: After controlling for gender, nicotine group status alone was not associated with neuropsychological performance. A gender x nicotine interaction was significantly associated with performance on trial 1, short delay free recall, and long delay free recall of the CVLT-II. Female smokers demonstrated better performance on trial 1 and short and long delay free recall than female controls. Male smokers performed more poorly than male controls on short and long delay free recall. Conclusions: These preliminary findings suggest that cognitive effects of chronic nicotine use are moderated by gender. Further research is needed to determine causality, and identify underlying brain structures and function that may be responsible for differences in verbal memory.

Varenicline and GZ-793A differentially decrease methamphetamine self-administration under a multiple schedule of reinforcement in rats.

Methamphetamine is a potent psychostimulant with high abuse rates. Currently, there is no Food and Drug Administration-approved pharmacotherapy for methamphetamine addiction. Ideally, a pharmacotherapy should selectively decrease methamphetamine self-administration without affecting responding for other reinforcers. One way to test this is with the use of a multiple schedule of reinforcement, in which drug and food are available in alternating components within a session. The present study evaluated GZ-793A, a vesicular monoamine transporter-2 inhibitor, and varenicline, a partial agonist at α4ß2 and full agonist at α7 nicotinic acetylcholine receptors, for their ability to decrease methamphetamine and food self-administration using a multiple schedule of reinforcement. Male Sprague-Dawley rats self-administered methamphetamine (0.03 mg/kg/intravenous infusion) and food pellets under a multiple schedule of reinforcement. GZ-793A or varenicline was administered before multiple schedule sessions. GZ-793A (5 and 20 mg/kg) significantly decreased methamphetamine intake compared with saline and did not alter food-maintained responding. In contrast, varenicline decreased methamphetamine intake less specifically across time. The results suggest that vesicular monoamine transporter-2 inhibition may be a viable pharmacological target for the treatment of methamphetamine-use disorders.

Nicotine Effects on White Matter Microstructure in Young Adults.

OBJECTIVE: Nicotine use is widely prevalent among youth, and is associated with white matter microstructural changes as measured by diffusion tensor imaging (DTI). In adults, nicotine use is generally associated with lower fractional anisotropy (FA), but in adolescents/young adults (≤30 years), microstructure appears healthier, indicated by higher FA. This cross-sectional study examined associations between nicotine use and white matter microstructure using fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD), and radial diffusivity (RD) in young adults. METHODS: Fifty-three participants (18 nicotine users [10 female]/35 controls [17 female]) ages 18-25 underwent MRI scan, neuropsychological battery, toxicology screening, and drug use interview. Nicotine group associations with FA and MD were examined in various white matter tracts. In significant tracts, AD and RD were measured. Exploratory correlations were conducted between significant tracts and verbal memory and sustained attention/working memory performance. RESULTS: Nicotine users exhibited significantly lower FA than controls in the left anterior thalamic radiation, left inferior longitudinal fasciculus, left superior longitudinal fasciculus-temporal, and left uncinate fasciculus. In these tracts, AD and RD did not differ, nor did MD differ in any tract. White matter quality was positively correlated with sustained attention/working memory performance. CONCLUSIONS: Cigarette smoking may disrupt white matter microstructure. These results are consistent with adult studies, but inconsistent with adolescent/young adult studies, likely due to methodological and sample age differences. Further studies should examine longitudinal effects of nicotine use on white matter microstructure in a larger sample.

Effects of environmental enrichment on d-amphetamine self-administration following nicotine exposure.

Adolescent nicotine exposure has been shown to lead to further psychostimulant use in adulthood. Previous preclinical research in rats has shown that environmental enrichment may protect against drug abuse vulnerability. The current study was designed to examine whether environmental enrichment can block the ability of adolescent nicotine exposure to increase d-amphetamine self-administration in adulthood. Male Sprague-Dawley rats were raised in either enriched conditions (ECs) or isolated conditions (ICs) and then injected with saline or nicotine (0.4 mg/kg, sc) for 7 days during adolescence. In adulthood rats were allowed to self-administer d-amphetamine under a fixed ratio (FR; 0, 0.006, 0.01, 0.02, 0.06, and 0.1 mg/kg/infusion) and progressive ratio (PR; 0, 0.006, 0.06, and 0.1 mg/kg/infusion) schedule of reinforcement. Nicotine-treated IC rats self-administered more d-amphetamine at 0.006, 0.01, and 0.02 mg/kg/infusion doses compared with their saline-treated IC counterparts regardless of the schedule maintaining behavior. This effect of nicotine was reversed in EC rats on a fixed ratio schedule. These findings indicate that environmental enrichment can limit the ability of adolescent nicotine exposure to increase vulnerability to other psychostimulant drugs, such as d-amphetamine. (PsycINFO Database Record

The effects of environmental enrichment on nicotine condition place preference in male rats.

Environmental enrichment has previously been shown to alter sensitivity to psychostimulants and opiates in various preclinical models. However, little research has been conducted studying the effects of environmental enrichment on the more commonly abused drug, nicotine. The current study raised male rats in either enriched conditions (EC) or isolated conditions (IC) and tested the animals' sensitivity to acquisition, extinction and reinstatement of nicotine conditioned place preference (CPP). Using a 3-chamber CPP apparatus, male Sprague-Dawley rats were conditioned with 1 of 3 doses of nicotine (0.4, 0.6, and 0.8 mg/kg) or saline on alternating days across 8 conditioning trials, followed by a test day for a nicotine-induced CPP response. Next, the animals had 5 extinction sessions followed by a nicotine-primed reinstatement session. EC rats displayed nicotine CPP at all 3 doses, whereas IC rats failed to show significant nicotine CPP relative to saline controls. EC rats also showed extinction of the nicotine-induced CPP response by the fifth extinction session for all 3 nicotine doses tested. However, only the 2 highest doses of the nicotine prime reinstated a CPP response in EC rats relative to saline controls. Taken together, these findings suggest that environmental enrichment may increase sensitivity to the rewarding effects of nicotine.