Adolescent rats are resistant to adaptations in excitatory and inhibitory mechanisms that modulate mesolimbic dopamine during nicotine withdrawal
Year: 2012
Type: article
Abstract: Adolescent smokers report enhanced positive responses to tobacco and fewer negative effects of withdrawal from this drug than adults, and this is believed to propel higher tobacco use during adolescence. Differential dopaminergic responses to nicotine are thought to underlie these age-related effects, as adolescent rats experience lower withdrawal-related deficits in nucleus accumbens (NAcc) dopamine versus adults. This study examined whether age differences in NAcc dopamine during withdrawal are mediated by excitatory or inhibitory transmission in the ventral tegmental area (VTA) dopamine cell body region. In vivo microdialysis was used to monitor extracellular levels of glutamate and gamma-aminobutyric acid (GABA) in the VTA of adolescent and adult rats experiencing nicotine withdrawal. In adults, nicotine withdrawal produced decreases in VTA glutamate levels (44% decrease) and increases in VTA GABA levels (38% increase). In contrast, adolescents did not exhibit changes in either of these measures. Naïve controls of both ages did not display changes in NAcc dopamine, VTA glutamate, or VTA GABA following mecamylamine. These results indicate that adolescents display resistance to withdrawal-related neurochemical processes that inhibit mesolimbic dopamine function in adults experiencing nicotine withdrawal. Our findings provide a potential mechanism involving VTA amino acid neurotransmission that modulates age differences during withdrawal.
Source: Journal of Neurochemistry
Language: English
Subfield: Physiology
Field: Medicine
Domain: Health Sciences
Open Access status: green
Awards: Border Biomedical Research Center, G3529779747, APA Diversity Program in Neuroscience, Mechanisms of developmental sensitivity to nicotine withdrawal, Sex Differences in the Mechanisms that Promote Nicotine Reward and Withdrawal, Endocannabinoid Metabolic Enzymes: Structure, Function, In Vivo Inhibition, Effect of nicotine self-administration on endocannabinoids & related lipids, G8191803414, Summer Mentoring and Research in Transdisciplinary Methodologies in Neuroscience of Drug-Addiction (SMART MIND)
OpenAlex ID: W2167223178