Evidence for a receptor supersensitivity following impairment of central serotoninergic activity in the rabbit.
In order to investigate whether a chronic impairment of neuronal serotoninergic transmission in the CNS could result in a receptor supersensitivity, rabbits were pretreated either with 5,6-dihydroxytryptamine (5,6-DHT) or p-chlorophenylalanine (PCPA) and then tested for their hyperthermic response to serotoninergic agonists. A previous (10 days before) intracerebroventricular injection of 5,6-DHT (75 microgram into each cerebral ventricle) significantly potentiated the increase in body temperature induced either by quipazine (1 mg/kg i.v.) or by 5-hydroxytryptophan (5-HTP 2 mg/kg i.v.) in combination with a MAO inhibitor (phenylethylhydrazine 10 mg/kg i.v. 16 h before). Pretreatment with PCPA (100 mg/kg s.c. four times on alternate days, the last dose 48 h before the experiment) also enhanced the hyperthermic effect of quipazine, whereas it inhibited the hyperthermic response to 5-HTP plus MAO inhibitor. These results suggest the existence of a receptor supersensitivity following prolonged blockade of serotoninergic neuronal transmission in the CNS.
D015115:5,6-Dihydroxytryptamine / Q000494:pharmacology; D006916:5-Hydroxytryptophan / Q000494:pharmacology; D000818:Animals; D001679:Biogenic Amines / Q000378:metabolism; D001831:Body Temperature / Q000187:drug effects; D010134:Fenclonine / Q000494:pharmacology; D008297:Male; D010659:Phenylhydrazines / Q000494:pharmacology; D011817:Rabbits; D011985:Receptors, Serotonin / Q000187:drug effects / Q000502:physiology*; D013997:Time Factors
D001679:Biogenic Amines; D010659:Phenylhydrazines; D011985:Receptors, Serotonin; D006916:5-Hydroxytryptophan; D010134:Fenclonine; D015115:5,6-Dihydroxytryptamine