A rat model of novelty-seeking phenotype predicts vulnerability to nicotine relapse where locomotor reactivity to novelty is used to rank high (HR) versus low (LR) responders. This dissertation examines the neuropeptidergic and structural substrates of the expression of locomotor sensitization to a low dose nicotine challenge and associated social anxiety-like behavior following chronic intermittent nicotine exposure during adolescence in the LRHR phenotype. Data show the long-lasting nature of behavioral sensitization to nicotine and abstinence-related social anxiety-like behavior in nicotine pre-trained HRs compared to saline pre-trained controls. Moreover, this behavior is accompanied by an imbalance between the brain antistress/antianxiety, i.e., neuropeptide Y (NPY), and stress, i.e., corticotrophin releasing factor (CRF) systems in the amygdala. Moreover, a deficit in NPY signaling marked with decreased NPY and increased NPY Y2 receptor (Y2R) mRNA levels is observed in the hip pocampus, along with mossy fiber reorganization in nicotine pre-trained HRs. Furthermore, a Y2R antagonist administered 1 wk of abstinence reverses these behavioral, molecular and morphological effects in nicotine-exposed HRs. Additionally, the role of amygdalar synaptic plasticity in longlasting social withdrawal is also investigated by assessing brain-derived neurotrophic factor (BDNF) and spinophilin mRNA levels in HRs following a behaviorally-sensitizing nicotine regimen. A persistent increase in BDNF and spinophilin mRNA levels in the basolateral amygdala (BLA) is observed in nicotine pre-trained HRs even across a long (3-wk) abstinence spanning into young adulthood. This strongly suggests BDNFmediated long-lasting neuroplasticity within the BLA that may regulate abstinence-related negative affect in HRs. / Moreover, a cannabinoid receptor 1 (CB1R) antagonist, AM251 treatment during a short (1-wk) abstinence is ineffective in reversing social anxiety, nicotine-induced neuroplasticity and the neuropeptidergic changes in the amygdala, although it is effective in reversing the expression of locomotor sensitization to challenge nicotine even following a long (3-wks) abstinence. Furthermore, the identical AM251 treatment given during the late phase of a long (3-wk) abstinence further augments social withdrawal and associated BLA plasticity in nicotine pre-trained HRs. These findings implicate neuropeptidergic and neuroplastic changes in the hippocampus and the amygdala in vulnerability to the long-lasting behavioral effects of nicotine in the novelty-seeking phenotype. / by Cigdem Aydin. / Thesis (Ph.D.)--Florida Atlantic University, 2011. / Includes bibliography. / Electronic reproduction. Boca Raton, Fla., 2011. Mode of access: World Wide Web.
| Identifer | oai:union.ndltd.org:fau.edu/oai:fau.digital.flvc.org:fau_3753 |
| Contributors | Aydin, Cigdem., Charles E. Schmidt College of Science, Department of Biological Sciences |
| Publisher | Florida Atlantic University |
| Source Sets | Florida Atlantic University |
| Language | English |
| Detected Language | English |
| Type | Text, Electronic Thesis or Dissertation |
| Format | xiii, 177 p. : ill. (some col.), electronic |
| Rights | http://rightsstatements.org/vocab/InC/1.0/ |
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