Antiparkinsonian effects of caffeine depend upon pavlovian drug conditioning processes

Caffeine induces the antiparkinsonian response of contralateral rotation in rats with unilateral 6-hydroxydopamine (6-OHDA) lesions following exposure to the direct-acting dopamine agonist apomorphine. This effect of caffeine has been attributed to a 'priming' effect of apomorphine which enables the supersensitive dopamine receptors to respond to caffeine and other methylxanthines. These studies, however, did not differentiate between conditioning and pharmacological variables. To resolve this issue, a Pavlovian conditioning procedure was employed in which separate groups of 6-OHDA rats were given 0.05 mg/kg (s.c.) apomorphine treatments paired or unpaired with a test environment. The animals in the paired or conditioning treatment groups subsequently exhibited contralateral rotation when tested with caffeine (10 mg/kg, i.p.), whereas animals in the unpaired or 'priming' treatment groups displayed only enhanced ipsilateral rotation. The activation of the conditioned contralateral rotation by caffeine in the paired group occurred even after the response was suppressed by extinction. This preferential activation following extinction of a previously conditioned drug response by caffeine implicates caffeine mechanisms (e.g. adenosine antagonism) in drug conditioning processes.