Temporal effects of nicotine and ethanol combined exposure on cholinergic system of the adolescent brain / Curso temporal dos efeitos da exposição combinada de nicotina e etanol no sistema colinérgico cerebral durante adolescência

AUTOR(ES)
DATA DE PUBLICAÇÃO

2009

RESUMO

Nicotine and ethanol are the most commonly consumed drugs. As clearly indicated by epidemiological studies, there is a close interrelationship between smoking and alcohol consumption manly during adolescence period. However, there are few studies on the basic neurobiology of the effects of the combined nicotine and ethanol exposure in the adolescent brain. Since nicotine is a cholinergic agonist and it has been shown that ethanol interferes with nicotinic acetylcholine receptors (nAChR), the current proposal will focus on the cholinergic effects of nicotine and/or ethanol treatment during adolescence. From the 30th to the 45th postnatal day (PN), C57BL/6 mice were exposed to nicotine free base (NIC) and/or ethanol (ETOH). Four groups were analyzed: 1) concomitant (NIC+ETOH) exposure of nicotine (50 μg/ml) and ethanol (25%, 2 g/kg i.p. every other day); 2) NIC exposure; 3) ETOH exposure; 4) vehicle. We assessed nAChR (α4β2) binding, choline acetyltransferase (ChAT) activity and [3H]hemicholinium-3 (HC-3) binding to the high affinity presynaptic choline transporter at the end of exposure period (PN45), at short (PN50) and long term (PN75) withdrawal. At the end of exposure period, NIC+ETOH elicited a pronounced upregulation which reflect simple additivity of the effects of nicotine and ethanol in the cerebral cortex and synergism in the midbrain. On PN45, male NIC mice presented an increase in ChAT in the cerebral cortex. However, ETOH reversed this effect. In contrast, female NIC mice presented decreased ChAT activity. In the midbrain, ETOH increased ChAT. On PN50, NIC mice presented an increase in ChAT activity that was reversed by ETOH withdrawal. In addition, NIC+ETOH long term withdrawal elicited a decrease in ChAT activity. Regarding HC-3, binding was not affected on PN45. ETOH and NIC+ETOH withdrawal promoted a decrease at short and long-term withdrawal. These results provide experimental evidences that nicotine and ethanol during adolescence interact resulting in cholinergic system alterations during exposure and withdrawal.

ASSUNTO(S)

sistema colinérgico adolescence nicotina etanol etanol nicotina sistema colinérgico neurofisiologia adolescência - álcool alcohol

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