The K‐Opioid Agonist, U‐69593, Decreases Acute Amphetamine‐Evoked Behaviors and Calcium‐Dependent Dialysate Levels of Dopamine and Glutamate in the Ventral Striatum

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Abstract
: The effect of a k‐opioid receptor agonist on acute amphetamine‐induced behavioral activation and dialysate levels of dopamine and glutamate in the ventral striatum were investigated. Amphetamine (2.5 mg/kg i.p.) evoked a substantial increase in rearing, sniffing, and hole‐poking behavior as well 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 increase in behavior and dopamine and glutamate levels in the ventral striatum. Reverse dialysis of the selective k‐opioid receptor antagonist, nor‐binaltorphimine, into the ventral striatum antagonized the effects of U‐69593 on amphetamine‐induced behavior and dopamine and glutamate levels. Reverse dialysis of low calcium (0.1 mM) into the ventral striatum decreased basal dopamine, but not glutamate, dialysate levels by 91% 45 min after initiation of perfusion. Strikingly, 0.1 mM calcium perfusion significantly reduced the 2.5 mg/kg amphetamine‐evoked increase in dopamine and glutamate levels in the ventral striatum, distinguishing a calcium‐dependent and a calcium‐independent component of release. U‐69593 did not alter the calcium‐independent component of amphetamine‐evoked dopamine and glutamate levels. These data are consistent with the view that a transsynaptic mechanism augments the increase in dopamine and glutamate levels in the ventral striatum evoked by a moderately high dose of amphetamine and that stimulation of k‐opioid receptors suppresses the calcium‐dependent component of amphetamine’s effects.

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