Dopamine D1 receptors and adenosine A1 receptors in the rat nucleus accumbens regulate motor activity but not prepulse inhibition.

Locomotor activity and sensorimotor gating (measured as prepulse inhibition of startle) are regulated by mesoaccumbal dopamine. Recent evidence indicated antagonistic interactions between adenosine A(1) receptors and dopamine D(1) receptors, as well as between adenosine A(2) receptors and dopamine D(2) receptors in the nucleus accumbens. Therefore, it is conceivable that accumbal dopamine and adenosine are both involved in the regulation of prepulse inhibition and locomotion. We tested whether accumbal adenosine A(1) and dopamine D(1) receptors control locomotor activity and prepulse inhibition using the following four treatments. (1) Injections of the selective adenosine A(1) receptor agonist N(6)-cyclopentanyladenosine (CPA 1.5 and 3 microg/microl per side) into the nucleus accumbens. (2) Stimulation of the ventral tegmental area by local infusion of the GABA(A) receptor antagonist picrotoxin (25-100 ng/0.5 microl bilaterally). (3) Picrotoxin injections into the ventral tegmental area (100 ng/0.5 microl) and simultaneous bilateral injections of CPA (3 microg/microl per side) into the nucleus accumbens. (4) Injections of the selective dopamine D(1) receptor antagonist SCH 23390 (3 microg/0.5 microl per side) into the nucleus accumbens and ventral tegmental area stimulation by picrotoxin. Intra-accumbal CPA infusion reduced locomotor activity but had no effect on prepulse inhibition. Picrotoxin stimulation of the ventral tegmental area increased locomotor activity which was antagonized by co-administration of CPA or SCH 23390 into the nucleus accumbens. An enhancement of prepulse inhibition was observed after stimulation of the ventral tegmental area and co-administration of SCH 23390 into the nucleus accumbens. These findings demonstrate that adenosine A(1) and dopamine D(1) receptors are involved in the regulation of locomotor activity mediated by the mesoaccumbal dopamine system. The finding that locomotor effects induced by stimulation of the mesoaccumbal dopamine system were not accompanied by a prepulse inhibition-deficit suggests a dissociation of the neuronal substrates involved in the control of locomotion and the regulation of sensorimotor gating.