EFFECT OF 4-PHENYL-1,2,3,4-TETRAHYDROISOQUINOLINE ON AMBULATION INDUCED BY INJECTION OF METHAMPHETAMINE INTO THE NUCLEUS-ACCUMBENS IN RATS

4-Phenyl-1,2,3,4-tetrahydroisoquinoline (4-PTIQ) has previously been shown to have antagonistic properties to methamphetamine in the spinal cord. Administration of 4-PTIQ (5 mg/kg, s.c.) reduced the ambulation induced by methamphetamine (0.5 mg/kg, s.c.) in rats. Methamphetamine (3 mug), injected unilaterally into the nucleus accumbens, increased ambulation. Alone, 4-PTIQ (10 mug) failed to elicit ambulation; however, it inhibited the methamphetamine-induced increase in ambulation. The alpha1-antagonist prazosin (0.5 mug) or the beta-antagonist propranolol (3 mug) showed no effect on ambulation induced by methamphetamine. Haloperidol (5 ng), which possesses strong dopamine-blocking activity, abolished the ambulation induced by methamphetamine. The drug 4-PTIQ had weak affinity for dopamine D1 and D2 receptors. These results support the possibility that the inhibitory effects of 4-PTIQ on the ambulation-stimulating effects of methamphetamine, are due to blocking of the dopamine-releasing effect of methamphetamine but not due to dopamine blocking effects.