Involvement of somatodendritic 5-HT1A receptors in Delta(9)-tetrahydrocannabinol-induced hypothermia in the rat

Previously, it has been reported that modulating serotonergic neurones by u se of selective serotonin reuptake inhibitors (SSRI) can alter the hypother mic response produced by Delta (9)-tetrahydrocannabinol (Delta (9)-THC). Th e aim of the present study was to investigate the effect that activation or antagonism of 5-hydroxytryptamine (5-HTIA) receptors has on Delta (9)-THC- induced hypothermia. Delta (9)-THC (0.5, 2 and 5 mg/kg iv) decreased body t emperature in a dose-related manner. Whilst having no significant effect on body temperature when administered 40 min prior to vehicle injection, the 5-HTIA receptor antagonist N-[2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl]-N -(2-pyridinyl) cyclohexane-carboxamide trihydrochloride (WAY 100635; 1 mg/k g sc) significantly potentiated the hypothermia produced by 2 and 5 mg/kg D elta (9)-THC. In order to investigate whether this effect was due to antago nism at somatodendritic autoreceptors in midbrain raphe nuclei, WAY 100635 or the 5-HTIA agonist 8-hydroxy-(di-n-propylamino) tetralin (8-OH-DPAT) was microinjected into either the median raphe nuclei (MRN) or dorsal raphe nu clei (DRN) 40 min prior to Delta (9)-THC injection. Following microinjectio n into the DRN, neither WAY 100635 (0.5 nmol/0.5 mul/10 s) nor 8-OH-DPAT (1 5.2 nmol/0.5 mul/10 s) had any significant effect on Delta (9)-THC-induced hypothermia. However, WAY 100635 when microinjected into the MRN significan tly potentiated Delta (9)-THC-induced hypothermia, and 8-OH-DPAT microinjec ted into the MRN significantly inhibited Delta (9)-THC-induced hypothermia. It is suggested from these studies that the potentiation of Delta (9)-THC- induced hypothermia by WAY 100635 when administered peripherally is mainly due to antagonism at somatodendritic 5-HTIA autoreceptors in the MRN. (C) 2 001 Elsevier Science Inc. All rights reserved.