Cytisine, a partial agonist of high-affinity nicotinic acetylcholine receptors, has antidepressant-like properties in male C57BL/6J mice.
The nicotine in tobacco is thought to modulate neuronal systems regulating mood. Moreover, it appears possible that blockade rather than activation of beta2-containing (beta2*) nicotinic acetylcholine receptors (nAChRs) may lead to antidepressant-like effects. We used cytisine, a partial agonist of alpha4/beta2*nAChRs and a full agonist at alpha3/beta4*nAChRs, in several tests of antidepressant efficacy. Further, we used c-fos expression to identify potential neurobiological correlates of the antidepressant-like effects of cytisine. Cytisine had antidepressant-like effects in several animal models of antidepressant efficacy. In addition, immunohistochemical analyses indicated that cytisine could reduce c-fos immunoreactivity in the basolateral amygdala by approximately 50%. These data show that cytisine acts like classical antidepressants in rodent models of antidepressant efficacy. In addition, cytisine's ability to block alpha4/beta2*nAChRs may be responsible for its antidepressant-like properties, and these may be mediated through a reduction of neuronal activity in the basolateral amygdala. These studies also suggest that both antagonists and partial agonists of alpha4/beta2*nAChRs would be interesting targets for the development of novel antidepressant drugs.
Mineur
Yann S
YS
Department of Psychiatry, Yale University School of Medicine, 34 Park Street, 3rd Floor Research, New Haven, CT 06508, USA.
Somenzi
Oli
O
Picciotto
Marina R
MR
D000470:Alkaloids / Q000494:pharmacology*; D000818:Animals; D000928:Antidepressive Agents; D001007:Anxiety / Q000523:psychology; D001392:Azocines / Q000494:pharmacology; D001921:Brain / Q000473:pathology; D003863:Depression / Q000473:pathology* / Q000523:psychology*; D005247:Feeding Behavior / Q000187:drug effects; D015870:Gene Expression / Q000187:drug effects; D016762:Genes, fos / Q000187:drug effects; D019417:Hindlimb Suspension / Q000523:psychology; D007150:Immunohistochemistry; D008297:Male; D008464:Mecamylamine / Q000494:pharmacology; D051379:Mice; D008810:Mice, Inbred C57BL; D009043:Motor Activity / Q000187:drug effects; D018722:Nicotinic Agonists / Q000494:pharmacology*; D011807:Quinolizines / Q000494:pharmacology; D011976:Receptors, Muscarinic / Q000187:drug effects*; D013550:Swimming / Q000523:psychology; D000093843:Quinolizidine Alkaloids
D000470:Alkaloids; D000928:Antidepressive Agents; D001392:Azocines; D008464:Mecamylamine; D018722:Nicotinic Agonists; D011807:Quinolizines; D011976:Receptors, Muscarinic; C004712:cytisine; D000093843:Quinolizidine Alkaloids