Blockade of D1 dopamine receptors in the medial prefrontal cortex attenuates amphetamine- and methamphetamine-induced locomotor activity in the rat.
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 microg) 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-HT(2C) 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 microg) and the 5-HT(2C) antagonist RS 102221 (0.25 microg) prior to METH (1 mg/kg, i.p.). The addition of the 5-HT(2C) 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.
Hall
Darien A
DA
Department of Psychology and Neuroscience Program, University of Illinois at Urbana-Champaign, 731 Psychology Bldg MC-716, 603 E Daniel St, Champaign, IL 61820, USA.
Powers
John P
JP
Gulley
Joshua M
JM
D000661:Amphetamine / Q000494:pharmacology; D000704:Analysis of Variance; D000818:Animals; D001552:Benzazepines / Q000494:pharmacology; D002408:Catheters, Indwelling; D004298:Dopamine / Q000378:metabolism; D015259:Dopamine Agents / Q000494:pharmacology; D018492:Dopamine Antagonists / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D006948:Hyperkinesis / Q000139:chemically induced* / Q000188:drug therapy*; D008297:Male; D008694:Methamphetamine / Q000494:pharmacology; D009043:Motor Activity / Q000187:drug effects* / Q000502:physiology; D017397:Prefrontal Cortex / Q000187:drug effects* / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D017447:Receptors, Dopamine D1 / Q000502:physiology*; D011985:Receptors, Serotonin / Q000502:physiology; D012702:Serotonin Antagonists / Q000494:pharmacology; D013141:Spiro Compounds / Q000494:pharmacology; D013449:Sulfonamides / Q000494:pharmacology
C107821:8-(5-(5-amino-2,4-dimethoxyphenyl)-5-oxopentyl)-1,3,8-triazaspiro(4.5)decane-2,4-dione; D001552:Benzazepines; D015259:Dopamine Agents; D018492:Dopamine Antagonists; D017447:Receptors, Dopamine D1; D011985:Receptors, Serotonin; C534628:SCH 23390; D012702:Serotonin Antagonists; D013141:Spiro Compounds; D013449:Sulfonamides; D008694:Methamphetamine; D000661:Amphetamine; D004298:Dopamine