Hypothermia induced by infusion of methionine sulfoximine into the dorsal raphe nucleus of the rat: involvement of 5-HT1A and GABAB receptors.
L-Methionine-D,L-sulfoximine (MSO) (25 micrograms) infused locally into the dorsal raphe nucleus (DRN) induced a progressive decrease in body temperature in conscious restrained rats kept at an ambient temperature of 23 degrees C. Pretreatment with (+/-)-pindolol (3 mg/kg s.c.) significantly attenuated MSO-induced hypothermia, but pretreatment with ketanserin (0.5 mg/kg i.p.) did not alter either the magnitude or the time course of the decrease in body temperature after intra-DRN infusion of MSO. Local accumulation of gamma-aminobutyric acid (GABA) after infusion of gamma-vinylGABA (10 micrograms) and (+/-)-nipecotic acid (6 micrograms) inhibited MSO-induced hypothermia. Blockade of GABAA receptors by infusion of (-)-bicuculline (25 ng) had no effect on the decrease in body temperature elicited by MSO, but blockade of GABAB receptors by infusion of 2-OH-saclofen (13.3 ng) significantly attenuated MSO-induced hypothermia. In conclusion, local infusion of MSO into the DRN must have slowed down the rate of 5-HT turnover in serotonergic neurons and decreased the release and synthesis of GABA. 5-HT1A somato-dendritic autoreceptors and GABAB postsynaptic receptors both appear to be involved in these neurocytochemical processes leading to hypothermia.
Ginefri-Gayet
M
M
Laboratoire de Physiologie Générale, Faculté des Sciences, Université de Nancy, Vandoeuvre-lès-Nancy, France.
Gayet
J
J
D000612:4-Aminobutyrate Transaminase / Q000037:antagonists & inhibitors; D000614:Aminocaproates / Q000494:pharmacology; D000818:Animals; D001418:Baclofen / Q000031:analogs & derivatives / Q000494:pharmacology; D001640:Bicuculline / Q000494:pharmacology; D001833:Body Temperature Regulation / Q000187:drug effects / Q000502:physiology; D007035:Hypothermia / Q000139:chemically induced*; D007263:Infusions, Parenteral; D007650:Ketanserin / Q000494:pharmacology; D008297:Male; D008717:Methionine Sulfoximine / Q000008:administration & dosage / Q000494:pharmacology*; D009557:Nipecotic Acids / Q000494:pharmacology; D010869:Pindolol / Q000494:pharmacology; D011392:Proline / Q000031:analogs & derivatives*; D011903:Raphe Nuclei / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D011963:Receptors, GABA-A / Q000187:drug effects* / Q000378:metabolism; D011985:Receptors, Serotonin / Q000187:drug effects* / Q000378:metabolism; D020888:Vigabatrin
D000614:Aminocaproates; D009557:Nipecotic Acids; D011963:Receptors, GABA-A; D011985:Receptors, Serotonin; D008717:Methionine Sulfoximine; C030278:nipecotic acid; D007650:Ketanserin; D011392:Proline; D010869:Pindolol; C010983:homoproline; D000612:4-Aminobutyrate Transaminase; D020888:Vigabatrin; D001418:Baclofen; C057491:2-hydroxysaclofen; D001640:Bicuculline