Behavioural and electoencephalographic interactions between haloperidol and PCP/sigma ligands in the rat.
Phencyclidine (PCP) and sigma ligands produce a typical excitatory behaviour in rats, characterized by circling and head- and body-weaving. Excitatory amino acid antagonists such as 2-amino 5-phosphonovaleric acid (AP5) or 3-(+/-)-2-carboxypiperazin-4-yl)propyl-l-phosphonic acid (CPP) also produce a PCP-like excitatory behaviour in rats. In the present paper, the interactions between PCP/sigma drugs or excitatory amino acid receptor antagonists and haloperidol have been investigated in rats. In addition, the influence of two other butyrophenones having a different affinity for the sigma/haloperidol receptors, such as spiperone and 3-(4-(3(4-fluorobenzoyl)-propyl-piperazino-l-yl-isoquinolino (HR 375), has been tested on the behavioural and EEG effects of PCP/sigma drugs and excitatory amino acid antagonists. PCP (2.5-5 mg/kg IP), (+) or (-) SKF 10,047 (1-15 mg/kg IP), (+) or (-) cyclazocine (2-8 mg/kg IP) and AP5 (0.5 mumol ICV) dose-dependently and significantly (P less than 0.01) antagonized the haloperidol-induced catalepsy in the horizontal bar and podium tests in rats. On the other hand, either haloperidol (1 mg/kg IP) or spiperone (1 mg/kg IP) reduced the head-weaving induced by (+) SKF 10,047, PCP, or AP5. On the contrary, HR 375 (6 mg/kg IP) was ineffective in blocking the excitatory effects of these drugs. In addition, either haloperidol (1 mg/kg IP) or spiperone (1 mg/kg IP), but not HR 375 (6 mg/kg IP) reduced the amplitude increase of the fast (20-30 Hz) frequency/low (30-50 microV) voltage background cortical activity elicited by PCP or (+) SKF 10,047. The results demonstrate an interaction between dopamine and excitatory amino acid receptors.(ABSTRACT TRUNCATED AT 250 WORDS)
Pharmacology Department, Istituto Superiore di Sanità, Roma, Italy.
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Sagratella
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Scotti de Carolis
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Pèzzola
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Popoli
D015763:2-Amino-5-phosphonovalerate / Q000494:pharmacology; D000704:Analysis of Variance; D000818:Animals; D014150:Antipsychotic Agents / Q000494:pharmacology; D001522:Behavior, Animal / Q000187:drug effects* / Q000502:physiology; D002375:Catalepsy / Q000139:chemically induced; D004569:Electroencephalography / Q000187:drug effects*; D006220:Haloperidol / Q000494:pharmacology*; D007546:Isoquinolines / Q000494:pharmacology; D007700:Kinetics; D008297:Male; D010620:Phenazocine / Q000031:analogs & derivatives / Q000494:pharmacology; D010622:Phencyclidine / Q000494:pharmacology*; D010879:Piperazines / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D016194:Receptors, N-Methyl-D-Aspartate / Q000187:drug effects; D011957:Receptors, Opioid / Q000187:drug effects*; D017480:Receptors, sigma; D013134:Spiperone / Q000494:pharmacology
D014150:Antipsychotic Agents; D007546:Isoquinolines; D010879:Piperazines; D016194:Receptors, N-Methyl-D-Aspartate; D011957:Receptors, Opioid; D017480:Receptors, sigma; D013134:Spiperone; C012134:SK&F 10047; D015763:2-Amino-5-phosphonovalerate; C051009:HR 375; D010620:Phenazocine; D010622:Phencyclidine; D006220:Haloperidol