Effects of intraaccumbens administration of SCH-23390 on cocaine-induced locomotion and conditioned place preference.

The effects of systemic (0-1.0 mg/kg) or intraaccumbens (0-1.0 microg/side) administration of SCH-23390 on cocaine-induced (0 or 4.2 mg/kg, i.v.) locomotion, sniffing, and conditioned place preference (CPP) were investigated in rats. After behavioral testing was completed, animals were injected with their respective dose of SCH-23390 into the nucleus accumbens (NAc), followed by a systemic injection of the irreversible antagonist N-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline (EEDQ). Receptors occupied by intraaccumbens SCH-23390, and therefore protected from EEDQ-induced inactivation, were then quantified from autoradiograms of sections labeled with 3H-SCH-23390. Systemic administration of 0.5 and 1.0 mg/kg SCH-23390 reversed cocaine-induced locomotion, sniffing, and CPP, suggesting that stimulation of D1-like receptors is necessary for these behavioral changes. Intraaccumbens administration of 1.0 microg/side SCH-23390 reversed cocaine-CPP, and this dose occupied D1-like receptors primarily in the rostral pole of the NAc. Intraaccumbens administration of 0.5 microg/side SCH-23390 reversed cocaine-induced locomotion. However, this dose occupied a similar number of D1-like receptors in the NAc as a lower and behaviorally ineffective dose of 0.1 microg/side, but occupied more receptors in the caudate-putamen relative to both the 0.1 and 1.0 microg/side doses. These findings suggest that stimulation of D1-like receptors in the NAc is necessary for cocaine-CPP, but not for cocaine-induced locomotion.

Amphetamine infused into the ventrolateral striatum produces oral stereotypies and conditioned place preference.

The effects of amphetamine infused into the ventrolateral striatum (VLS) on locomotion, stereotypies, and conditioned place preference (CPP) were investigated. Five 2-day conditioning trials were conducted over 10 consecutive days. On 1 day of each trial, animals received an infusion of amphetamine (0, 2.5, 5, 10, or 20 mg/0.5 ml/side) and were placed into a distinct compartment for 30 min. On the other day, animals received sham intracranial infusions and were placed into a different compartment for 30 min. Locomotion and stereotypies were assessed following the first and last amphetamine infusions. CPP was assessed the day following the last conditioning trial. Intra-VLS infusions of amphetamine did not alter sniffing or locomotion. Acute administration of amphetamine into the VLS dose dependently produced oral stereotypies, however, tolerance developed to this effect following repeated administrations. Also, intra-VLS infusions of amphetamine dose dependently produced CPP. These results suggest that the VLS is involved in amphetamine-induced oral stereotypies and reward.

Predictive validity of the extinction/reinstatement model of drug craving.

The effects of chronic desmethylimipramine (DMI) treatment on measures of incentive motivation for cocaine were assessed in order to investigate the predictive validity of the extinction/reinstatement model of drug craving. Rats were trained to respond for cocaine infusions (0.75 mg/kg per 0.1 ml i.v.) or received yoked-saline infusions during daily 3-h sessions. A light and tone were presented with the infusions. Following self-administration training, each group received daily injections of either saline or DMI (10 mg/kg, i.p.) for 21 days of withdrawal from the self-administration regimen. On days 12-21 of withdrawal, rats were allowed to respond in the absence of cocaine reinforcement (extinction phase). After reaching an extinction criterion of no responses for 1 h, the cocaine-paired stimuli were repeatedly presented to reinstate responding (reinstatement phase). In the control group, DMI treatment did not alter responding during either test phase, but increased the response latency during the extinction phase. In contrast, DMI treatment in the cocaine group decreased responding and increased the response latency during both test phases, and decreased the extinction latency during the extinction phase. Overall, the effects of DMI were consistent with a reduction of incentive motivation for cocaine, lending support for the predictive validity of the extinction/reinstatement model of drug craving.