Cocaine self-administration is not dependent upon mesocortical α1 noradrenergic signaling

Abstract

The rewarding properties of psychomotor stimulants are traditionally thought to be independent of norepinephrine. Recent findings, however, suggest that local noradrenergic signaling through α1 receptors in the medial prefrontal cortex and the ventral tegmental area - brain regions critically important in natural and drug rewards - is in a position to influence stimulant reward. Despite this controversy, the contribution of this targeted signaling to stimulant self-administration has not been directly assessed. We have thus examined whether pharmacological blockade of α1 receptors in the medial prefrontal cortex and ventral tegmental area alters cocaine self-administration. Rats were trained to lever-press for cocaine (1.0 mg/kg/infusion) under a fixed ratio 1 schedule of reinforcement for 10 days. After training, the rats received a bilateral microinjection of an α1 noradrenergic antagonist (terazosin: 1.0, 5.0, or 10 mM/side), a D1 dopaminergic antagonist (SCH23390: 12.3 mM/side), or saline into either the medial prefrontal cortex or ventral tegmental area immediately before a cocaine self-administration session. Although SCH23390 significantly increased cocaine self-administration when injected into either brain region, terazosin, at all doses and sites tested, failed to alter this behavior. Thus, the maintenance of cocaine self-administration appears to be under the influence of D1 dopaminergic, rather than α1 noradrenergic, signaling at these mesocortical sites.