The comparative pharmacology of the behavioral syndromes induced by TRH and by 5-HT in the rat.
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. 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. 5-HTP potentiated MK-771-induced hyperthermia. 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. MK-771-induced shaking behavior was pharmacologically dissociated from other MK-771-evoked behaviors. A 5-HT1A agonist (8-OH-DPAT) blocked WDS, but like putative 5-HT1B (RU 24969) and 5-HT2 (DOI) agonists and the 5-HT antagonists methysergide (non-selective), ritanserin (5-HT2 selective), and l-propranolol (5-HT1 selective), it did not block other antagonists behavioural effects of MK-771. 6. Ipsapirone, a 5-HT1A-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. 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. These data suggest behavioral relatedness of the TRH and 5-HT syndromes, but distinctive pharmacologic features and presumed mechanisms of action.
D015116:5,7-Dihydroxytryptamine / Q000494:pharmacology; D006916:5-Hydroxytryptophan / Q000494:pharmacology; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; D000818:Animals; D014151:Anti-Anxiety Agents / Q000494:pharmacology; D000928:Antidepressive Agents / Q000494:pharmacology; D001522:Behavior, Animal / Q000187:drug effects*; D001831:Body Temperature / Q000187:drug effects; D002946:Cisterna Magna; D007267:Injections; D008297:Male; D011743:Pyrimidines / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D012701:Serotonin / Q000494:pharmacology*; D013764:Tetrahydronaphthalenes / Q000494:pharmacology; D053778:Thiazolidines; D013973:Thyrotropin-Releasing Hormone / Q000031:analogs & derivatives / Q000494:pharmacology*
D014151:Anti-Anxiety Agents; D000928:Antidepressive Agents; D011743:Pyrimidines; D013764:Tetrahydronaphthalenes; D053778:Thiazolidines; D015116:5,7-Dihydroxytryptamine; D012701:Serotonin; D013973:Thyrotropin-Releasing Hormone; C021597:pyro(l-alpha-aminoadipyl)-L-histidyl-L-thiazolidine-4-carboxamide; C043077:ipsapirone; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; D006916:5-Hydroxytryptophan