title: Possible involvement of sigma-1 receptors in the anti-immobility action of bupropion, a dopamine reuptake inhibitor.
abstract: Sigma receptors particularly, sigma-1 subtype is known to modulate the release of catecholamines in the brain and may participate in the mechanism of action of various antidepressants. The present study investigated the possible involvement of sigma receptors in modulating the anti-immobility-like effect of bupropion (a dopamine reuptake inhibitor) using the forced swim test (FST) in mice. Bupropion produced dose-dependent (10-40 mg/kg, i.p.) reduction in immobility period and the ED(50) value was found to be 18.5 (7.34-46.6) mg/kg, i.p. (+)-Pentazocine (2.5 mg/kg, i.p.), a high-affinity sigma-1 receptor agonist, produced synergistic response when it was co-administered with a subeffective dose of bupropion (10 mg/kg, i.p.). On the contrary, pretreatment with progesterone (10 mg/kg, s.c.), a sigma-1 receptor antagonist neurosteroid, rimcazole (5 mg/kg, i.p.), another sigma-1 receptor antagonist, or BD 1047 (1 mg/kg, i.p.), a novel sigma-1 receptor antagonist, reversed the anti-immobility effects of bupropion (20 mg/kg, i.p.). The various modulators used in the study did not show any effect per se on locomotor activity except bupropion which at a higher dose (15-40 mg/kg, i.p.) significantly increased the locomotor activity. The results for the first time demonstrated the involvement of sigma-1 receptors in the anti-immobility effects of bupropion.
authors.affiliation: Pharmacology Division, University Institute of Pharmaceutical Sciences, Panjab University, Chandigarh 160014, India.
authors.forename: Ashish
authors.initials: A
authors.lastname: Dhir
authors.forename: S K
authors.initials: SK
authors.lastname: Kulkarni
mesh_terms: D000701:Analgesics, Opioid / Q000494:pharmacology; D000818:Animals; D018687:Antidepressive Agents, Second-Generation / Q000494:pharmacology*; D001522:Behavior, Animal / Q000187:drug effects; D016642:Bupropion / Q000494:pharmacology*; D002227:Carbazoles / Q000494:pharmacology; D018765:Dopamine Uptake Inhibitors / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D005029:Ethylenediamines / Q000494:pharmacology; D008297:Male; D051379:Mice; D009043:Motor Activity / Q000187:drug effects*; D018696:Neuroprotective Agents / Q000494:pharmacology; D010423:Pentazocine / Q000494:pharmacology; D011374:Progesterone / Q000494:pharmacology; D017480:Receptors, sigma / Q000819:agonists* / Q000037:antagonists & inhibitors*; D013315:Stress, Psychological / Q000188:drug therapy; D000097605:Sigma-1 Receptor
chemical_list: D000701:Analgesics, Opioid; D018687:Antidepressive Agents, Second-Generation; D016642:Bupropion; D002227:Carbazoles; D018765:Dopamine Uptake Inhibitors; D005029:Ethylenediamines; D018696:Neuroprotective Agents; D010423:Pentazocine; D011374:Progesterone; D017480:Receptors, sigma; D000097605:Sigma-1 Receptor; C097963:N-(2-(3,4-Dichlorphenyl)ethyl)-N,N',N'-trimethyl-1,2-ethandiamin; C034931:rimcazole