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Clozapine Reverses Hyperthermia and Sympathetically Mediated Cutaneous Vasoconstriction Induced by M

Clozapine Reverses Hyperthermia and Sympathetically Mediated Cutaneous Vasoconstriction Induced by M

  1. Jatelka
    Journal of Neuroscience 2003 Jul 16;23(15):6385-91

    Blessing WW, Seaman B, Pedersen NP , Ootsuka Y .

    Life-threatening hyperthermia occurs in some individuals taking 3,4-methylenedioxymethamphetamine (MDMA, ecstasy). In rabbits, sympathetically mediated vasoconstriction in heat-exchanging cutaneous beds (ear pinnae) contributes to MDMA-elicited hyperthermia. We investigated whether MDMA-elicited cutaneous vasoconstriction and hyperthermia are reversed by clozapine and olanzapine, atypical antipsychotic agents. Ear pinna blood flow and body temperature were measured in conscious rabbits; MDMA (6 mg/kg, i.v.) was administered; and clozapine (0.1-5 mg/kg, i.v.) or olanzapine (0.5 mg/kg, i.v.) was administered 15 min later. One hour after MDMA, temperature was 38.7 +/- 0.5 degrees C in 5 mg/kg clozapine-treated rabbits and 39.0 +/- 0.2 degrees C in olanzapine-treated rabbits, less than untreated animals (41.5 +/- 0.3 degrees C) and unchanged from pre-MDMA values. Ear pinna blood flow increased from the MDMA-induced near zero level within 5 min of clozapine or olanzapine administration. Clozapine-induced temperature and flow responses were dose-dependent. In urethane-anesthetized rabbits, MDMA (6 mg/kg, i.v.) increased ear pinna postganglionic sympathetic nerve discharge to 217 +/- 33% of the pre-MDMA baseline. Five minutes after clozapine (1 mg/kg, i.v.) discharge was reduced to 10 +/- 4% of the MDMA-elicited level. In conscious rats made hyperthermic by MDMA (10 mg/kg, s.c.), body temperature 1 hr after clozapine (3 mg/kg, s.c.) was 36.9 +/- 0.5 degrees C,