Effects of repeated ropinirole treatment on phencyclidine-induced hyperlocomotion, prepulse inhibition deficits, and social avoidance in rats

Amanda M. Maple, Tanessa Call, Phylicia C. Kimmel, Ronald P. Hammer

Research output: Contribution to journalArticle

4 Scopus citations

Abstract

Phencyclidine (PCP), a noncompetitive N-methyl D-aspartate (NMDA) receptor antagonist, provides the most complete pharmacologic model of schizophrenia in humans and animals. Acute PCP causes hyperlocomotion, disrupts prepulse inhibition (PPI), and increases social avoidance in rats. We have previously shown that repeated treatment with the dopamine (DA) D2-like receptor agonists, quinpirole or ropinirole, prevents agonist-induced PPI disruption. In the present study, we examined whether repeated ropinirole treatment similarly attenuates the effects of PCP in a more complete model of schizophrenia symptoms and examined the effect of repeated D2-like agonist treatment on locomotion, PPI, and social interaction after acute PCP challenge. The acute effect of PCP (3.0 or 6.0 mg/kg) on locomotor activity was examined to establish a minimum effective dose. Thereafter, the effect of PCP challenge (3.0 mg/kg) on locomotor activity, PPI, and social interaction was assessed in adult male rats before or 7-10 days after termination of repeated daily treatment with ropinirole (0.1 mg/kg) or saline vehicle (0.1 ml/kg) for 28 days. Repeated ropinirole treatment attenuates PCP-induced hyperlocomotion, PPI deficits, and social avoidance. These findings suggest that repeated ropinirole treatment might affect a final common pathway that is vulnerable to both PCP- and dopamine agonist-induced behavioral disruption, thereby providing an alternative approach to block the effects of PCP.

Original languageEnglish (US)
Pages (from-to)109-114
Number of pages6
JournalJournal of Pharmacology and Experimental Therapeutics
Volume361
Issue number1
DOIs
StatePublished - Apr 2017

ASJC Scopus subject areas

  • Molecular Medicine
  • Pharmacology

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