Amino acid modulation of dopamine in the nucleus accumbens mediates sex differences in nicotine withdrawal
Autor: | Luis A. Natividad, Laura E. O'Dell, Rodolfo J. Flores, Luis M. Carcoba |
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Rok vydání: | 2017 |
Předmět: |
0301 basic medicine
Pharmacology medicine.medical_specialty Chemistry Kindling Dopaminergic Glutamate receptor Medicine (miscellaneous) Nucleus accumbens medicine.disease 03 medical and health sciences Psychiatry and Mental health 030104 developmental biology 0302 clinical medicine Nicotine withdrawal Nicotinic agonist Endocrinology Dopamine Internal medicine Mecamylamine medicine 030217 neurology & neurosurgery medicine.drug |
Zdroj: | Addiction Biology. 23:1046-1054 |
ISSN: | 1355-6215 |
DOI: | 10.1111/adb.12556 |
Popis: | The aversive effect of nicotine withdrawal is greater in female versus male rats, and we postulate that this sex difference is mediated in the nucleus accumbens (NAc). Nicotine withdrawal induces decreases in NAc dopamine and increases in acetylcholine (ACh) levels in male rats. To our knowledge, these neurochemical markers of nicotine withdrawal have not been compared in female versus male rats. Given the role of amino acids in modulating NAc dopaminergic and cholinergic transmission, concomitant measures of gamma-aminobutyric acid (GABA) and glutamate levels were also compared across sex. Rats received continuous nicotine exposure for 14 days, and then NAc dialysate was collected during baseline and following administration of the nicotinic receptor antagonist mecamylamine to precipitate withdrawal. Chronic nicotine exposure was associated with larger increases in baseline dopamine, GABA and glutamate levels in the NAc of female versus male rats, whereas baseline ACh was only increased in male rats. During withdrawal, both sexes displayed equivalent increases in NAc ACh levels. As expected, male rats displayed decreases in dopamine, coupled with increases in GABA and decreases in glutamate levels, suggesting the possibility of increased inhibitory tone in the NAc during withdrawal. Relative to males, female rats displayed larger decreases in NAc dopamine and related increases in GABAergic transmission. As female rats also showed elevated glutamate levels that persist during withdrawal, it is suggested that sex differences may arise from increased glutamatergic drive of inhibitory tone in the NAc. The findings provide a potential mechanism whereby the aversive effects of nicotine withdrawal are enhanced in female rats. |
Databáze: | OpenAIRE |
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