title: Enhancement of serotonin-1A receptor dependent responses following withdrawal of haloperidol in rats.
abstract: Although haloperidol is widely prescribed for the treatment of schizophrenia, its beneficial effects are accompanied by extrapyramidal side effects (EPS). In view of a role of 5-hydroxytryptamine (5-HT; serotonin)-1A receptors in the elicitation of EPS, the present study concerns pre- and postsynaptic responses to a selective 5-HT-1A receptor agonist, 8-hydroxy-2-(di-n-propylamino) tetralin (8-OH-DPAT) following acute and chronic administration of haloperidol in rats. In the acute administration study, effects of 8-OH-DPAT (0.5 mg/kg) were monitored 30 min after single injection of haloperidol (5 mg/kg). In the chronic administration study, effects of 8-OH-DPAT (0.5 mg/kg) were monitored 48 h after withdrawal from repeated (two times a day for 2 weeks) administration of haloperidol (5 mg/kg). The intensity of 5-HT syndrome elicited by 8-OH-DPAT was taken as measure of postsynaptic response. 8-OH-DPAT-induced decreases of 5-HT synthesis were taken as measure of presynaptic response. Results showed that 8-OH-DPAT-induced locomotion was smaller in acute haloperidol-treated rats. Conversely, these effects of 8-OH-DPAT were greater in chronic haloperidol-treated rats. Animals injected acutely or chronically with haloperidol exhibited greater 5-HT synthesis in the striatum. Administration of 8-OH-DPAT did not decrease 5-HT synthesis in the striatum of acute haloperidol-treated rats but decreased it in the striatum of chronic haloperidol-treated rats. The results show an increase in the effectiveness of pre- and postsynaptic 5-HT-1A receptor dependent responses following chronic administration of haloperidol. A causal role of 5-HT-1A receptor responsiveness in the greater incidences of EPS in patients treated with typical neuroleptics such as haloperidol is discussed.
authors.affiliation: Department of Biochemistry, Neurochemistry and Biochemical Neuropharmacology Research Laboratory, University of Karachi, Karachi, 75270, Pakistan. haleemdj@hotmail.com
authors.forename: Darakhshan Jabeen
authors.initials: DJ
authors.lastname: Haleem
authors.forename: Nadia Hasan
authors.initials: NH
authors.lastname: Khan
mesh_terms: D017371:8-Hydroxy-2-(di-n-propylamino)tetralin / Q000494:pharmacology*; D000818:Animals; D001480:Basal Ganglia Diseases / Q000209:etiology / Q000503:physiopathology*; D018492:Dopamine Antagonists / Q000008:administration & dosage / Q000009:adverse effects*; D004334:Drug Administration Schedule; D006220:Haloperidol / Q000008:administration & dosage / Q000009:adverse effects*; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D011985:Receptors, Serotonin / Q000502:physiology*; D044263:Receptors, Serotonin, 5-HT1; D017366:Serotonin Receptor Agonists / Q000494:pharmacology*; D013375:Substance Withdrawal Syndrome; D009435:Synaptic Transmission
chemical_list: D018492:Dopamine Antagonists; D011985:Receptors, Serotonin; D044263:Receptors, Serotonin, 5-HT1; D017366:Serotonin Receptor Agonists; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; D006220:Haloperidol