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Adolescent rats are resistant to adaptations in excitatory and inhibitory mechanisms that modulate mesolimbic dopamine during nicotine withdrawal
Author(s) -
Natividad Luis A.,
Buczynski Matthew W.,
Parsons Loren H.,
Torres Oscar V.,
O'Dell Laura E.
Publication year - 2012
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.2012.07926.x
Subject(s) - ventral tegmental area , dopamine , nicotine withdrawal , nucleus accumbens , neurochemical , dopaminergic , nicotine , microdialysis , glutamate receptor , mesolimbic pathway , excitatory postsynaptic potential , neuroscience , inhibitory postsynaptic potential , psychology , medicine , endocrinology , receptor
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 ( NA cc) dopamine versus adults. This study examined whether age differences in NA cc 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 NA cc 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.