title: Contribution of the central histaminergic transmission in the cataleptic and neuroleptic effects of haloperidol.
abstract: The antipsychotic properties of haloperidol are primarily attributed to its ability to block dopamine D2 receptors. Histaminergic transmission modulates some of the behavioral effects of haloperidol. Hence, the present study investigated the contribution of central histaminergic transmission in the cataleptic and neuroleptic effect of haloperidol respectively, using bar test and conditioned avoidance response (CAR) in a two-way shuttle box. The studies revealed that haloperidol (0.50 or 1 mg/kg, i.p.) exhibited cataleptic behavior and inhibited conditioned avoidance response (CAR) in the doses 0.25 or 0.50 mg in rats. The rats, pretreated centrally (i.c.v.) with histamine precursor, L-histidine (1, 2.5 μg) or histamine neuronal inducer (H3 receptor antagonist), thioperamide (20, 50 μg/rat), showed an enhanced cataleptic effect with sub-maximal dose of haloperidol (0.5 mg/kg, i.p.). Similarly, the neuroleptic effect of haloperidol (0.25 mg/kg, i.p.) in CAR was also potentiated in the rats pretreated with L-histidine (2.5 μg) or thioperamide (50 μg/rat). Further, the cataleptic effect of haloperidol (1 mg/kg, i.p.) was attenuated in rats pretreated with the H1 receptor antagonist, chlorpheniramine (60, 80 μg/rat, i.c.v.) or H2 receptor antagonist, ranitidine (60 μg/rat, i.c.v.). However, the neuroleptic effect of haloperidol (0.5 mg/kg, i.p.) was completely reversed by pretreatment with ranitidine (60 μg/rat, i.c.v.), and partially attenuated by chlorpheniramine (80 μg/rat, i.c.v.). These findings suggest the possible involvement of histaminergic transmission in the cataleptic and neuroleptic effects of haloperidol probably via H1 or H2 receptor stimulation.
authors.affiliation: Department of Pharmacology, Institute of Pharmaceutical Sciences, Guru Ghasidas University (A Central University), Koni, Bilaspur, Chhattisgarh, India. Electronic address: nishant.s.jain@hotmail.com.
authors.forename: Nishant S
authors.initials: NS
authors.lastname: Jain
authors.affiliation: Department of Pharmacology, Institute of Pharmaceutical Sciences, Guru Ghasidas University (A Central University), Koni, Bilaspur, Chhattisgarh, India.
authors.forename: Lakshyapati
authors.initials: L
authors.lastname: Tandi
authors.affiliation: Department of Pharmacology, Institute of Pharmaceutical Sciences, Guru Ghasidas University (A Central University), Koni, Bilaspur, Chhattisgarh, India.
authors.forename: Lokesh
authors.initials: L
authors.lastname: Verma
mesh_terms: D000818:Animals; D014150:Antipsychotic Agents / Q000008:administration & dosage / Q000494:pharmacology*; D001362:Avoidance Learning / Q000187:drug effects; D002375:Catalepsy / Q000139:chemically induced* / Q000188:drug therapy / Q000378:metabolism*; D002744:Chlorpheniramine / Q000008:administration & dosage / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D006220:Haloperidol / Q000008:administration & dosage / Q000494:pharmacology*; D006632:Histamine / Q000378:metabolism*; D017442:Histamine Agonists / Q000008:administration & dosage / Q000494:pharmacology; D006639:Histidine / Q000008:administration & dosage / Q000494:pharmacology; D057967:Infusions, Intraventricular; D008297:Male; D010880:Piperidines / Q000008:administration & dosage / Q000494:pharmacology; D011899:Ranitidine / Q000008:administration & dosage / Q000494:pharmacology; D051381:Rats; D011968:Receptors, Histamine / Q000378:metabolism; D009435:Synaptic Transmission / Q000187:drug effects
chemical_list: D014150:Antipsychotic Agents; D017442:Histamine Agonists; D010880:Piperidines; D011968:Receptors, Histamine; D002744:Chlorpheniramine; D006639:Histidine; D006632:Histamine; D011899:Ranitidine; C052075:thioperamide; D006220:Haloperidol
keywords: Antipsychotic effects; Catalepsy; Conditioned avoidance chamber; Haloperidol; Histamine; Neuroleptics