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

详细信息    查看全文

• 作者：Darien A. Hall ; John P. Powers ; Joshua M. Gulley
• 关键词：Open-field activity ; Serotonin ; SCH 23390 ; RS 102221 ; D1 receptor antagonist ; 5-HT_2C receptor antagonist
• 刊名：Brain Research
• 出版年：2009
• 出版时间：10 November 2009
• 年：2009
• 卷：1300
• 期：Complete
• 页码：51-57
• 全文大小：442 K

文摘

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-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 μg) and the 5-HT_2C antagonist RS 102221 (0.25 μg) 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.