Blockade of D1 dopamine receptors in the medial prefrontal cortex attenuates amphetamine- and methamphetamine-induced locomotor activity in the rat

Darien A. Hall, John P. Powers, Joshua M. Gulley

Research output: Contribution to journalArticle

Abstract

The medial prefrontal cortex (mPFC) is a component of the mesolimbic dopamine (DA) system involved in psychostimulant-induced hyperactivity and previous studies have shown that altering DA transmission or D2 receptors within the mPFC can decrease this stimulant effect. The goal of this study was to investigate a potential modulatory role for D1 receptors in the mPFC in amphetamine (AMPH)- and methamphetamine (METH)-induced hyperactivity. Locomotor activity in an open-field arena was measured in male, Sprague-Dawley rats given an intra-mPFC infusion of vehicle or the D1 receptor antagonist SCH 23390 (0.25 or 1.0 μg) prior to systemic (i.p.) injection of saline, AMPH (1 mg/kg), or METH (1 mg/kg). We found that SCH 23390 produced a dose-dependent decrease in AMPH- and METH-induced locomotion and rearing but had no significant effect on spontaneous behavior that occurred following systemic saline injections. Because SCH 23390 has been shown to have agonist-like properties at 5-HT2C receptors, a follow-up experiment was performed to determine if this contributed to the attenuation of METH-induced activity that we observed. Rats were given intra-mPFC infusions of both SCH 23390 (1.0 μg) and the 5-HT2C antagonist RS 102221 (0.25 μg) prior to METH (1 mg/kg, i.p.). The addition of the 5-HT2C antagonist failed to alter SCH 23390-induced decreases in METH-induced locomotion and rearing; infusion of RS 102221 alone had no significant effects on locomotion and produced a non-significant decrease in rearing. The results of these studies suggest that D1 activation in the mPFC plays a significant role in AMPH- and METH-induced hyperactivity.

Original languageEnglish (US)
Pages (from-to)51-57
Number of pages7
JournalBrain Research
Volume1300
DOIs
StatePublished - Nov 10 2009

Keywords

  • 5-HT receptor antagonist
  • D1 receptor antagonist
  • Open-field activity
  • RS 102221
  • SCH 23390
  • Serotonin

ASJC Scopus subject areas

  • Neuroscience(all)
  • Molecular Biology
  • Clinical Neurology
  • Developmental Biology

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