Lack of synergism between caffeine and SKF 38393 on rotational behavior in 6-hydroxydopamine-denervated rats

Abstract

We have recently shown a synergistic effect between caffeine and the dopamine D 2 receptor agonist, bromocriptine, on contralateral rotational behavior in unilaterally 6-hydroxydopamine-denervated rats. In addition, we found that bromocriptine prevented caffeine-induced tolerance to this behavior following repeated treatment. In the present study, we investigated whether or not the dopamine D 1 receptor agonist, (±)-phenyl-2,3,4,5-tetrahydro-(1 H)-3-benzazepine-7,8-diol (SKF 38393), presented similar characteristics. Different groups of rats received simultaneous injections of either vehicle plus vehicle, caffeine (40 mg/kg) plus vehicle, SKF 38393 (0.5, 1, 2, and 4 mg/kg) plus vehicle, or caffeine plus SKF 38393 (0.5, 1, 2, and 4 mg/kg) for 5 consecutive days, and both ipsilateral and contralateral rotational behavior was measured. Results showed that, on the first day of treatment, caffeine produced significantly more rotational behavior than did a low dose of SKF 38393 (0.5 mg/kg), and significantly less turning than at higher doses (2 and 4 mg/kg). Combined treatment with caffeine and a high dose of SKF 38393 (4 mg/kg) produced significantly more rotational behavior than did caffeine plus vehicle. With repeated administration, caffeine produced sustained tolerance to its effects on rotational behavior, whereas SKF 38393 did not. In the groups treated with low doses of SKF 38393 (0.5, and 1 mg/kg) plus caffeine, tolerance was observed while in the groups that received high doses of SKF 38393 (2 and 4 mg/kg) plus caffeine, no tolerance was observed to rotational behavior. These results suggest that maximal stimulation of dopamine D 1 receptors may be needed to prevent the tolerance effects of caffeine in this animal model. This finding may have clinical relevance to the therapeutic treatment of Parkinson's disease.