Behavioural and electoencephalographic interactions between haloperidol and PCP/sigma ligands in the rat

Psychopharmacology (Berl). 1991;105(4):485-91. doi: 10.1007/BF02244368.

Abstract

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)

Publication types

  • Comparative Study

MeSH terms

  • 2-Amino-5-phosphonovalerate / pharmacology
  • Analysis of Variance
  • Animals
  • Antipsychotic Agents / pharmacology
  • Behavior, Animal / drug effects*
  • Behavior, Animal / physiology
  • Catalepsy / chemically induced
  • Electroencephalography / drug effects*
  • Haloperidol / pharmacology*
  • Isoquinolines / pharmacology
  • Kinetics
  • Male
  • Phenazocine / analogs & derivatives
  • Phenazocine / pharmacology
  • Phencyclidine / pharmacology*
  • Piperazines / pharmacology
  • Rats
  • Rats, Inbred Strains
  • Receptors, N-Methyl-D-Aspartate / drug effects
  • Receptors, Opioid / drug effects*
  • Receptors, sigma
  • Spiperone / pharmacology

Substances

  • Antipsychotic Agents
  • Isoquinolines
  • Piperazines
  • Receptors, N-Methyl-D-Aspartate
  • Receptors, Opioid
  • Receptors, sigma
  • Spiperone
  • SK&F 10047
  • 2-Amino-5-phosphonovalerate
  • HR 375
  • Phenazocine
  • Phencyclidine
  • Haloperidol