RESUMO
Depression is currently the most popular disease in the world with a high suicide rate. Selective 5-HT reuptake inhibitors have been used as first-line drugs in clinics, but the therapeutic effect is greatly limited. The pathogenesis of depression is complicated, meanwhile the cholinergic hypothesis has received more and more attention. A large number of clinical and preclinical studies have shown that antagonists and partial agonists acting on nicotinic acetylcholine receptors have a significant effect on antidepressant therapy, which can improve the hippocampus recognizes, influence rewards and anxiety systems controlled by the ventral midbrain and ventral tegmental area, and regulate the amygdala pressure system, thereby improving mood and relieving depression. At present, the relationship between the cholinergic system and depression is still undergoing a lot of research. In this article, the relationship between α4β2 nicotinic acetylcholine receptor (nAChRs) and depression is reviewed to provide a reference for study of new anti-depression drugs.
RESUMO
OBJECTIVE Individuals vary in sensitivity to the behavioral effects of nicotine, resulting in differences in their vulnerability to addiction. The role of rearing environment in determining individual sensitivity to nicotine is unclear. The neuropharmacological mechanisms mediating the effect of rearing environment on the actions of nicotine are also understood. Thus, the contribution of rearing environment in determining the sensitivity to the locomotor effects of nicotine and regulating α4β2*- and α7-nicotinic acetylcholine (nACh) receptor expressionwas determined in rats reared in isolated (IC) or enriched (EC) conditions. METHODS To measure locomotor activity, adolescent rats (postnatal day 21- 51) were injected with saline (1 mL·kg-1) or nicotine (0.3 mg·kg-1) subcutaneously, then placed in chamber?swhere ambulatory activity was monitored for 30-min by computer for 14 daily sessions. α4β2*- andα7- nACh receptor expression in the mesolimbic dopamine pathway was determined by quantitative autoradiography of [125I]-epibatidine and [125I]-bungarotoxinbinding, respectively, in 16 μmol·L- 1 coronal sections. Values for receptor expression in fmol are x ± s of 8 brains and compared by two- tailed, unpaired t-test with P<0.05 considered significant. RESULTS EC-rats are similarly sensitive as IC-rats to the locomotor effects of nicotine. [125I]-epibatidine binding in the ventral tegmental area of EC-rats was reduced (2.8 ± 0.3 fmoL) compared to IC-rats (4.0 ± 0.4 fmoL); there was no difference in the nucleus accumbens. There was no difference between EC- and IC-rats in α7-nACh receptor expression in the mesolimbic dopamine pathway. CONCLUSION Rearing environment differentially regulates nACh receptor subtypes in EC and IC rats. These data suggest regulation of nACh receptors by environmental factors may be a mechanism for the protective effect of enrichment against altered sensi?tivity to nicotine in genetically vulnerable individuals. The characterization of these mechanisms will aid in development of novel pharmacological tools mimicking the protection afforded by environmental enrichment in nicotine-sensitive individuals.