Locomotion and conditioned place preference produced by acute intravenous amphetamine: role of dopamine receptors and individual differences in amphetamine self-administration

Abstract

Although previous studies have shown that dopamine (DA) antagonists block amphetamine reward, these studies have utilized animal models that involve repeated exposures to amphetamine. The present investigation examined the effect of DA antagonists on single-trial conditioned place preference (CPP) produced by acute intravenous (IV) amphetamine in rats. In the fi rst experiment, rats were prepared with a jugular catheter and then received an acute IV injection of amphetamine (0.1-3 mg/kg) paired with one compartment of a CPP apparatus. Relative to sham controls (no IV catheter), amphetamine produced a dose-dependent increase in locomotor activity and CPP. Two further experiments demonstrated that both effects of amphetamine were completely blocked by pretreating rats with the D 1 DA antagonist SCH-23390 (0.025 and 0.25 mg/kg) or the D 2 DA antagonist eticlopride (0.2 and 2 mg/kg) on the conditioning trial. In a fi nal experiment, single-trial amphetamine CPP did not predict subsequent self-administration of IV amphetamine (10-50 μg/infusion) using either a fi xed ratio (FR) 1 or progressive ratio (PR) schedule of reinforcement. Thus, while sharing a similar DA receptor mechanism, the present results indicate that single-trial CPP and self-administration are dissociable effects of IV amphetamine.

Reversal of Ethanol-Seeking Behavior by D1 and D2 Antagonists in an Animal Model of Relapse: Differences in Antagonist Potency in Previously Ethanol-Dependent versus Nondependent Rats

“…In contrast to D1 antagonists, D2-selective antagonist agents are more commonly associated with nonspecific deficits in motor performance . However, the dose range at which eticlopride induces motoric impairments is typically higher than that in the present study (Bardo et al, 1999;Bevins et al, 2001). In light of this literature as well as the absence of significant DA antagonist effects on responding in the S Ϫ condition, it seems unlikely that performance deficits contributed importantly to the attenuation of ethanol-seeking behavior by SCH23390 and eticlopride.…”

Withdrawal from Acute Amphetamine Induces an Amygdala-Driven Attenuation of Dopamine Neuron Activity: Reversal by Ketamine

“…Therefore, following chronic use, the positive affect following drug administration is followed by the opposite process to maintain homeostasis in brain systems: a negative affective state which has been advanced in the opponent process theory of motivation (for a review, see Koob and Le Moal, 2008). It has been hypothesized that this effect appears after the positive hedonic response following even initial acute drug administration (Bardo et al, 1999;Koob and Le Moal, 2008). As the majority of studies have investigated homeostatic changes following chronic drug use, in the present study we examined changes in VTA DA neuron activity in the acute phase after drug administration, which is proposed to predispose an individual to seeking and taking of drugs in the earliest phases of its use.…”

Conditioned Locomotion Is Not Correlated with Behavioral Sensitization to Cocaine An Intra-Laboratory Multi-Sample Analysis

“…These observations suggest that mechanisms underlying behavioral sensitization can be dissociated from those mediating drug-free conditioned responses. Other studies have shown that the degree of conditioned place preference to psychostimulants can be dissociated from unconditioned locomotor effects (Shimosato and Ohkuma 2000) and from self-administration behavior (Bardo et al 1999).…”