Cocaine-paired Cues Research Articles

Caffeine place conditioning in rats: comparison with cocaine and ethanol

The present study employed the place conditioning technique to compare rewarding potential of caffeine with that of cocaine and ethanol. In Experiment 1 caffeine, cocaine and ethanol place conditioning were estimated independently, whereas in Experiments 2 and 3 the preference of the external cues associated with caffeine vs. cocaine and caffeine vs. ethanol was assessed in a single test. Caffeine (1.5 mg/kg, i.p.) cocaine (5 mg/kg, i.p.) and ethanol (1.2 g/kg, i.g.) did produce secondary reinforcing effects comparable in magnitude (Experiment 1). In Experiments 2 and 3 animals had the opportunity `to compare' rewarding effects of two drugs. Data showed that the preference of cocaine-paired cues was absolutely (100%) higher than those of caffeine, whereas reinforcing actions of caffeine and ethanol seemed to be equal. The proposed modification of conditioned place preference procedure may be useful for the comparison of rewarding values of different drugs with presumed addictive potential.

Evidence for conditional neuronal activation following exposure to a cocaine-paired environment: role of forebrain limbic structures

The reinforcing properties of cocaine can readily become associated with salient environmental stimuli that acquire secondary reinforcing properties. This form of classical conditioning is of considerable clinical relevance as intense craving can be evoked by the presentation of stimuli previously associated with the effects of cocaine. To understand better the neurobiology of cocaine-induced environment-specific conditioning, Fos expression was examined in the forebrain of rats exposed to an environment in which they had previously received cocaine. These results were compared to those observed following an acute injection of cocaine. Consistent with its stimulant actions, cocaine produced an increase in locomotion that was accompanied by an increase in Fos expression within specific limbic regions (cingulate cortex, claustrum, piriform cortex, lateral septal nucleus, paraventricular nucleus of the thalamus, lateral habenula, and amygdala) as well as the basal ganglia (dorsomedial striatum and nucleus accumbens). Exposure of rats to the cocaine-paired environment also produced an increase in locomotion, as compared to various control groups. In addition to this behavioral effect, conditioned subjects exhibited a significant increase in Fos expression within the cingulate cortex, claustrum, lateral septal nucleus, paraventricular nucleus of the thalamus, lateral habenula, and the amygdala, suggesting increased neuronal activity within these regions. In contrast to the dramatic effects observed within these structures, no conditional activation was observed within the piriform cortex, nucleus accumbens, or dorsal striatum, suggesting that these brain areas are not involved in the conditioned response. The present findings indicate that specific limbic regions exhibit increased neuronal activation during the presentation of cocaine-paired cues and may be involved in the formation of associations between cocaine's stimulant actions and the environment in which the drug administration occurred. Although the nucleus accumbens is necessary for the reinforcing and locomotor effects of cocaine, it does not exhibit a conditional Fos response, suggesting that different neural circuits are involved in the unconditioned and conditioned effects of cocaine.