Despite this controversy, the contribution of this targeted signaling to stimulant self-administration Tanespimycin chemical structure has not been directly assessed. We have thus examined whether pharmacological blockade of alpha 1 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 alpha 1 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, PRT062607 chemical structure the maintenance of cocaine self-administration appears to be under the influence of D1 dopaminergic, rather than alpha 1 noradrenergic, signaling at these mesocortical sites. NeuroReport 23:325-330 (C) 2012 Wolters Kluwer Health vertical bar Lippincott

Williams & Wilkins.”
“Rationale The novel antipsychotic aripiprazole in use for treatment of schizophrenia is a partial agonist at dopamine D(2) receptors with actions at a variety of other receptors as well. Cocaine is believed to exert an important part of its rewarding effect Cyclosporin A cell line by increasing extracellular levels of dopamine that subsequently act at dopamine D2 receptors.

Objectives As a partial agonist, aripiprazole may antagonize effects at D(2) receptors and we accordingly tested whether aripiprazole could antagonize self-administration of cocaine. Because D(2)-like receptor agonists are self-administered, a D2 receptor partial agonist like aripiprazole might itself be reinforcing. Thus, we also assessed whether mice would acquire self-administration of aripiprazole.

Materials

and methods A single session, mouse self-administration procedure was used.

Results Oral pretreatment with aripiprazole dose-dependently decreased cocaine self-administration under a fixed ratio 1 schedule at the peak cocaine dose (0.03 mg/kg/infusion), reaching significance at 0.2 and 0.4 mg/kg of aripiprazole. Using 0.4 mg/kg, aripiprazole decreased rates of cocaine self-administration without shifting the peak of the dose-response function. There was no effect of aripiprazole per se, suggesting that its inhibitory action was due to effects on cocaine self-administration rather than non-specific motor effects. Aripiprazole was not found to be self-administered in the tested dose range (0.0003-0.3 mg/kg/infusion). The three highest doses (0.03, 0.1, and 0.