The comparative pharmacology of the behavioral syndromes induced by TRH and by 5-HT in the rat

Abstract

1. 1. The relationship of the behavioral syndromes induced by the co-transmitters thyrotropin releasing hormone (TRH) and serotonin (5-HT) has not been previously studied with drugs selective for 5-HT receptor subtypes. 2. 2. Both the TRH analog MK-771 (in naive rats) and 5-hydroxytryptophan (in rats with 5,7-dihydroxytryptamine [DHT] lesions) evoked reciprocal forepaw tapping, Straub tail, hunching, hindlimb abduction, and shaking behavior. Sniffing and rearing were features of the MK-771 but not the 5-HT syndrome. 3. 3. 5-HTP potentiated MK-771-induced hyperthermia. 4. 4. MK-771 evoked two types of shaking behavior, head shakes (HS) and wet-dog shakes (WDS). Neither independently was dose-related, unlike total shaking behaviors. 5. 5. MK-771-induced shaking behavior was pharmacologically dissociated from other MK-771-evoked behaviors. A 5-HT 1A agonist (8-OH-DPAT) blocked WDS, but like putative 5-HT 1B (RU 24969) and 5-HT 2 (DOI) agonists and the 5-HT antagonists methysergide (non-selective), ritanserin (5-HT 2 selective), and l-propranolol (5-HT 1 selective), it did not block other antagonists behavioural effects of MK-771. 6. 6. Insapirone, a 5-HT 1A-active drug purported both as an agonist and as an antagonist, inhibited MK-771-evoked WDS, like 8-OH-DPAT, but did not induce the serotonin syndrome, unlike 8-OH-DPAT. 7. 7. DHT-treated rats were behaviorally supersensitive to 10 mg/kg MK-771 as indicated by a significantly shortened latency of onset of WDS and greater frequency of abnormal forepaw movements. The same rats were also supersensitive to 50 mg/kg 5-HTP to a significantly greater degree. 8. 8. These data suggest behavioral relatedness of the TRH and 5-HT syndromes, but distinctive pharmacologic features and presumed mechanisms of action.