Resumo

Objectives: Repeated treatment with dopamine agonist stimulant drugs reliably induces sensitization effects. This sensitization effect is multifaceted in that it can include changes in neurotransmitter receptor sensitivity as well as learning/plasticity mechanisms such as Pavlovian conditioning. In the present work, the impact of extinction and counter-conditioning upon apomorphine conditioning and sensitization was studied. To induce conditioning and sensitization effects, the Pavlovian paired/unpaired treatment protocol was applied. Methods: The experiment consisted of two phases: an induction phase and an extinction phase. In each phase there was a pharmacological treatment, a conditioning test and a sensitization test. Male Wistar rats were submitted to the pharmacological treatment of the induction phase and were divided into the following groups: paired group (APO-2.0-P; n=18); unpaired group (APO-2.0-UP; n=6) and vehicle group (VEH; n=6). Treatments were administered on 5 consecutive days. After a withdrawal period of 2 days, the animals received an injection of saline before being placed into the arena (conditioning test), and following a second withdrawal period, the apomorphine challenge test was performed in which the animals from paired and unpaired groups received 2.0 mg/kg apomorphine. In the extinction phase, the animals from the APO-2.0-P group were divided into three sub-groups in which the first sub-group received 0.05 mg/kg apomorphine (APO-2.0-P+0.05-P; n=6); the second sub-group received 0.05 mg/kg apomorphine unpaired to the arena (APO-2.0-P+0.05-UP; n=6) and the third sub-group received vehicle associated to the arena (APO-2.0-P+VEH-P; n=6). The animals from the APO-2.0-UP group received 0.05 mg/kg apomorphine unpaired (APO-2.0-UP+0.05-UP; n=6) and the vehicle group received vehicle (VEH-VEH). Results: The initial repeated apomorphine 2.0 mg/kg treatments induced hyperlocomotion, generated a conditioned hyperlocomotion response and a sensitized apomorphine locomotion effect selectively in the paired groups. By using extinction and counter-conditioning procedures, it was showed that the conditioned locomotion stimulant response could be readily and reliably eliminated. While the counter-conditioning treatment suppressed locomotion more than extinction, in the extinction phase it was not more effective than extinction in eliminating the apomorphine conditioned hyper-locomotion response. The sensitized apomorphine locomotion response was insensitive to these extinction and counter-conditioning manipulations. Conclusion: The results showed that context dependent sensitization is a long lasting process and that conditioning contributes a little in this phenomenon, which suggests dissociation between the drug conditioning effects and the context dependent sensitization.