Enhancement of serotonin-1A receptor dependent responses following withdrawal of haloperidol in rats

• Published in: Progress in neuro-psychopharmacology & biological psychiatry 2003-06, Vol.27 (4), p.645-651
• Main Authors: Haleem, Darakhshan Jabeen, Khan, Nadia Hasan
• Format: Article
• Language: English
• Subjects: 5-HT syndrome; 5-HT synthesis; 8-Hydroxy-2-(di-n-propylamino)tetralin - pharmacology; 8-OH-DPAT; Animals; Basal Ganglia Diseases - etiology; Basal Ganglia Diseases - physiopathology; Biological and medical sciences; Dopamine Antagonists - administration & dosage; Dopamine Antagonists - adverse effects; Drug Administration Schedule; Drug intoxications. Doping; EPS; Haloperidol; Haloperidol - administration & dosage; Haloperidol - adverse effects; Male; Medical sciences; Pharmacology. Drug treatments; Rats; Rats, Wistar; Receptors, Serotonin - physiology; Receptors, Serotonin, 5-HT1; Serotonin Receptor Agonists - pharmacology; Substance Withdrawal Syndrome; Synaptic Transmission
• ISSN: 0278-5846; 1878-4216
• DOI: 10.1016/S0278-5846(03)00074-5

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.