title: Nicotine-induced anxiety-like behavior in a rat model of the novelty-seeking phenotype is associated with long-lasting neuropeptidergic and neuroplastic adaptations in the amygdala: effects of the cannabinoid receptor 1 antagonist AM251.
abstract: A rat model of the novelty-seeking phenotype predicts vulnerability to the expression of behavioral sensitization to nicotine, where locomotor reactivity to novelty is used to screen experimentally-naïve rats for high (HR) versus low (LR) responders. The present study examines the long-term neuropeptidergic and neuroplastic adaptations associated with the expression of locomotor sensitization to a low dose nicotine challenge and social anxiety-like behavior following chronic intermittent nicotine exposure during adolescence in the LRHR phenotype. Our data show that the expression of behavioral sensitization to nicotine and abstinence-related anxiety are detected in nicotine pre-exposed HRs even across a long (3 wks) abstinence. Moreover, these behavioral effects of nicotine are accompanied by a persistent imbalance between neuropeptide Y and corticotrophin releasing factor systems, and a persistent increase in brain-derived neurotrophic factor (BDNF) and spinophilin mRNA levels in the amygdala. Furthermore, treatment with the cannabinoid receptor 1 antagonist, AM251 (5 mg/kg) during a short (1 wk) abstinence is ineffective in reversing nicotine-induced anxiety, fluctuations in BDNF and spinophilin mRNAs, and the neuropeptidergic dysregulations in the amygdala; although this treatment is effective in reversing the expression of locomotor sensitization to challenge nicotine even after a long abstinence. Interestingly, the identical AM251 treatment administered during the late phase of a long abstinence further augments anxiety and associated changes in BDNF and spinophilin mRNA in the basolateral nucleus of the amygdala in nicotine pre-exposed HRs. These findings implicate long-lasting neuropeptidergic and neuroplastic changes in the amygdala in vulnerability to the behavioral effects of nicotine in the novelty-seeking phenotype.
authors.affiliation: Charles E. Schmidt College of Medicine, Department of Biomedical Science, Florida Atlantic University, 777 Glades Road, Boca Raton, FL 33431, USA.
authors.forename: Cigdem
authors.initials: C
authors.lastname: Aydin
authors.forename: Ozge
authors.initials: O
authors.lastname: Oztan
authors.forename: Ceylan
authors.initials: C
authors.lastname: Isgor
mesh_terms: D000375:Aging / Q000523:psychology; D000679:Amygdala / Q000187:drug effects*; D000818:Animals; D001007:Anxiety / Q000139:chemically induced* / Q000523:psychology*; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism; D003346:Corticotropin-Releasing Hormone / Q000378:metabolism; D005106:Exploratory Behavior / Q000187:drug effects*; D017403:In Situ Hybridization; D007398:Interpersonal Relations; D008297:Male; D008840:Microfilament Proteins / Q000378:metabolism; D009043:Motor Activity / Q000187:drug effects; D009419:Nerve Tissue Proteins / Q000378:metabolism; D009473:Neuronal Plasticity / Q000187:drug effects*; D009478:Neuropeptide Y / Q000378:metabolism; D009479:Neuropeptides / Q000502:physiology*; D009538:Nicotine / Q000494:pharmacology*; D018722:Nicotinic Agonists / Q000494:pharmacology*; D010641:Phenotype; D010880:Piperidines / Q000494:pharmacology*; D011720:Pyrazoles / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D043884:Receptor, Cannabinoid, CB1 / Q000037:antagonists & inhibitors*; D013375:Substance Withdrawal Syndrome / Q000523:psychology; D000099273:Neurabins
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D003346:Corticotropin-Releasing Hormone; D008840:Microfilament Proteins; D009419:Nerve Tissue Proteins; D009478:Neuropeptide Y; D009479:Neuropeptides; D009538:Nicotine; D018722:Nicotinic Agonists; D010880:Piperidines; D011720:Pyrazoles; D043884:Receptor, Cannabinoid, CB1; D000099273:Neurabins; C103505:AM 251