Sigma 1 receptor subtype is involved in the relief of behavioral despair in the mouse forced swimming test.
The immobility time in the mouse forced swimming test was dose-dependently reduced by sigma 1 receptor agonists, such as 1-(3,4-dimethoxyphenethyl)-4-(3-phenylpropyl)piperazine dihydrochloride (SA4503) and (+)-pentazocine, and non-specific sigma receptor agonists, such as 1,3-di(2-tolyl)guanidine (DTG) and (+)-N-cyclopropyl-methyl-N-methyl-1,4-diphenyl-1-yl-but-3-en-1-ylamin e hydrochloride (JO-1784). On the other hand, pre-treatment with N,N-dipropyl-2-[4-methoxy-3-(2-phenylethoxy)phenyl]ethylamine monohydrochloride (NE-100), a putative sigma 1 receptor antagonist, completely antagonized the SA4503-, (+)-pentazocine- and DTG-induced reductions in immobility time. Such phenomena indicate that sigma receptor agonists alleviate behavioral despair. In addition, these antidepressive effects involve mainly the sigma 1 receptor subtype.
Central Research Laboratories, Santen Pharmaceutical Co, Ltd, Osaka, Japan.
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Matsuno
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Kobayashi
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Tanaka
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Mita
D000818:Animals; D000840:Anisoles / Q000494:pharmacology; D002934:Cinnamates / Q000494:pharmacology; D003521:Cyclopropanes / Q000494:pharmacology; D006146:Guanidines / Q000494:pharmacology; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D009043:Motor Activity / Q000187:drug effects*; D010423:Pentazocine / Q000494:pharmacology; D010879:Piperazines / Q000494:pharmacology; D011437:Propylamines / Q000494:pharmacology; D017480:Receptors, sigma / Q000819:agonists / Q000037:antagonists & inhibitors / Q000378:metabolism*; D013312:Stress, Physiological / Q000378:metabolism*
D000840:Anisoles; D002934:Cinnamates; D003521:Cyclopropanes; D006146:Guanidines; D010879:Piperazines; D011437:Propylamines; D017480:Receptors, sigma; C083832:N,N-dipropyl-2-(4-methoxy-3-(2-phenylethoxy)phenyl)ethylamine monohydrochloride; C101789:SA 4503; C050232:1,3-ditolylguanidine; D010423:Pentazocine; C065310:igmesine