Theophylline-induced grooming: possible indirect dopaminergic mechanism

The ability of theophylline, an adenosine antagonist and phosphodiesterase inhibitor, to induce grooming was studied in rats. Grooming was induced by intraperitoneal (i.p.) injection of different doses (6-25 mg/kg) of theophylline to rats. The effect was dose-dependent. However, the response was decreased with increasing doses of the drug from 25-75 mg/kg. Administration of the dopamine D1 receptor agonist SKF 38393 (1-phenyl-7,8-dihydroxy-2,3,4,5-tetrahydro-1 H-3-benzazepine hydrochloride; 16 mg/kg i.p.) also caused grooming in a dose-dependent manner. The response induced by SKF 38393 (1-4 mg/kg i.p.) was decreased by the high doses of theophylline (50 and 75 mg/kg i.p.). The dopamine D1 receptor antagonist SCH 23390 (R-(+)-8-chloro-2,3,4,5-tetrahydro-3-methyl-5-phenyl-1 H-benzazepine-7-ol maleate) decreased the theophylline and SKF 38393 response. Pretreatment of animals with reserpine (2.5 mg/kg i.p., 24 h) reduced the effect of theophylline (12.5 and 25 mg/kg i.p.) but not that of SKF 38393 (1 and 4 mg/kg i.p.). It is concluded that theophylline elicits grooming through an indirect D1 dopaminergic mechanism.