Stimulant drugs as conditioned and unconditioned stimuli in a classical conditioning paradigm

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Abstract
A number of important ways in which drugs interact with learning processes have been identified in studies of the behavioral pharmacology of centrally active drugs. For example, drugs can act as discriminative and as reinforcement stimuli or as unconditioned stimuli eliciting unconditioned responses. Regarding the latter, it has been shown that a number of drug effects can be conditioned to exteroceptive stimuli, providing a mechanism by which drug effects can be transferred from the drug itself to external environment stimulus control. This paper focuses on the development of conditioned drug responses using drug‐induced rotational behavior in rats with unilateral lesions of dopamine neurons. A particularly useful advantage of this model is that the drug‐induced response is mediated by a specific central nervous system (CNS) substrate and the criterion rotational response is unambiguous and easily quantified. Additionally, different drugs can elicit the same response of rotation but in a different direction (i.e., depending on the drug used to induce rotation, ipsilateral or contralateral to the dopamine‐denervated hemisphere). This difference in directionality of drug‐induced rotation provides an opportunity to condition responses to different stimulant drugs differentially, which is not possible in the intact animal, since these drugs tend to evoke similar responses (e.g., hyperactivity or stereotypy). Another advantage of directionality differences in rotational responses associated with different stimulant drugs is that one can assess conditioning interactions between drugs. For example, if one drug that elicits an ipsilateral rotation is paired with another drug that elicits contralateral rotation, then, through a conditioning paradigm of paired drug presentations, one might shift the direction of rotation of the one drug used as the conditioned stimulus to that of the other drug used as the unconditioned stimulus. A number of procedures are described in which the anticholinergic drug scopolamine (which elicits ipsilateral rotation) is paired as the conditioned stimulus with the dopaminergic drug apomorphine (which elicits contralateral rotation) as the unconditioned stimulus, and, as a result, the scopolamine comes to elicit contralateral rotation when subsequently given alone. Observation of such effects points to the importance of drug–drug interactions influenced by Pavlovian conditioning processes.