REGULATION OF SENSORIMOTOR GATING BY INTERACTIONS OF DOPAMINE AND ADENOSINE IN THE RAT

Prepulse inhibition (PPI) of the acoustic startle response is a behavi oural tool used to assess sensorimotor gating processes and its distur bances in rats and in humans. PPI in rats is reduced by an overactivit y of the dopamine (DA) system. Because there are functional interactio ns between DA and adenosine receptors, we tested whether PPI can be in fluenced by the mixed DA receptor agonist apomorphine (APO) and by the unselective adenosine antagonist theophylline (THEO). Combined admini stration of APO (0.5 mg/kg, i.p.) and THEO (20 mg/kg, i.p.) in doses d evoid of significant effects on their own significantly reduced PPI. T he PPI-disrupting effect of the combined THEO plus APO treatment was d ose-dependently antagonized by co-administration of the selective aden osine A(1) agonist CPA (0.15 1.5 mg/kg, i.p.), but not by the A(2A) ag onist CGS21680 (0.1 2 mg/kg, i.p.). These data demonstrate that antago nistic interactions between DA and adenosine, involving adenosine A(1) receptors, play an important role in the regulation of PPI. The possi ble implications of these findings for the use of adenosine agonists i n the treatment of schizophrenia are discussed.