Cocaine conditioning and cocaine sensitization: what is the relationship?

Abstract

With repeated cocaine use, cocaine conditioned behavior develops to associated stimuli, and in addition, sensitization can occur to the unconditioned stimulant effects of cocaine. To investigate the relationship between the conditioned and unconditioned behavioral effects of repeated cocaine use, two groups of rats ( n=7) were given five daily paired cocaine treatments (10 mg/kg i.p.) immediately before a 20-min placement in an open-field environment. Other groups received either saline before testing or cocaine unpaired which was administered 30 min after testing in the homecage. When tested in the open-field with saline for conditioned effects, the two cocaine paired groups selectively exhibited substantial and equivalent cocaine conditioned responses. One of these groups was subjected to an extinction procedure which was effective in eliminating the cocaine conditioned responses. Subsequently, all the rats which had received cocaine in the first phase of the experiment, paired and unpaired, along with a subset of saline animals were given a cocaine (10 mg/kg i.p.) challenge test. The paired cocaine animals exhibited an earlier onset of the cocaine induced behavioral response (sensitization) as compared with the saline and the unpaired cocaine animals. Critically, the sensitization effects were unaffected by extinction, and in addition, the conditioned response did not contribute to the sensitization effect. It is suggested that the cocaine drug response occludes the cocaine conditioned response. Subsequent to this sensitization test, the animals were retested for conditioning. In this test, the paired cocaine animals which had not been subjected to the extinction procedure still exhibited a conditioned cocaine response, whereas, the paired cocaine group subjected to extinction was indistinguishable from saline controls. Although the present results show that Pavlovian conditioned responses to exteroceptive contextual cues do not directly contribute to cocaine induced behavioral sensitization effects, the sensitization effects were context-specific, and therefore, were tied to associative processes. It is suggested that context specificity is mediated by a compound stimulus complex comprised of exteroceptive stimuli and interoceptive cocaine drug cues. Furthermore, these exteroceptive and interoceptive cues associated with cocaine effectively expedite the onset of cocaine effects, and thereby, facilitate the addictive potency of cocaine.