The kappa-opioid agonist, U-69593, decreases acute amphetamine-evoked behaviors and calcium-dependent dialysate levels of dopamine and glutamate in the ventral striatum

The effects of a kappa-opioid receptor agonist on acute amphetamine-induced behavioral activation and dialysate levels of dopamine and glutamate in th e ventral striatum were investigated. Amphetamine (2.5 mg/kg i.p.) evoked a substantial increase in rearing, sniffing, and hole-poking behavior as wel l as dopamine and glutamate levels in the ventral striatum of awake rats. U -69593 (0.32 mg/kg s.c.) significantly decreased the amphetamine-evoked inc rease in behavior and dopamine and glutamate levels in the ventral striatum . Reverse dialysis of the selective kappa-opioid receptor antagonist, nor-b inaltorphimine, into the ventral striatum antagonized the effects of U-6959 3 on amphetamine-induced behavior and dopamine and glutamate levels. Revers e dialysis of low calcium (0.1 mM) into the ventral striatum decreased basa l dopamine, but not glutamate, dialysate levels by 91% 45 min after initiat ion of perfusion. Strikingly, 0.1 mM calcium perfusion significantly reduce d the 2.5 mg/kg amphetamine-evoked increase in dopamine and glutamate level s in the ventral striatum, distinguishing a calcium-dependent and a calcium -independent component of release. U-69593 did not alter the calcium-indepe ndent component of amphetamine-evoked dopamine and glutamate levels. These data are consistent with the view that a transsynaptic mechanism augments t he increase in dopamine and glutamate levels in the ventral striatum evoked by a moderately high dose of amphetamine and that stimulation of kappa-opi oid receptors suppresses the calcium-dependent component of amphetamine's e ffects.