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

• Published in: Journal of neurochemistry Vol. 73; no. 3; pp. 1066 - 1074
• Main Authors: GRAY, A. M, RAWLS, S. M, SHIPPENBERG, T. S, MCGINTY, J. F
• Format: Journal Article
• Language: English
• Published: Oxford Blackwell 01.09.1999
• Subjects: Amphetamine - antagonists & inhibitors; Amphetamine - pharmacology; Animals; Behavior, Animal - drug effects; Benzeneacetamides; Biological and medical sciences; Calcium - physiology; Dopamine - metabolism; Glutamic Acid - metabolism; Male; Medical sciences; Microdialysis; Naltrexone - analogs & derivatives; Naltrexone - pharmacology; Narcotic Antagonists - pharmacology; Neostriatum - drug effects; Neostriatum - metabolism; Neuropharmacology; Pharmacology. Drug treatments; Psychoanaleptics: cns stimulant, antidepressant agent, nootropic agent, mood stabilizer..., (alzheimer disease); Psychology. Psychoanalysis. Psychiatry; Psychopharmacology; Pyrrolidines - pharmacology; Rats; Rats, Wistar; Receptors, Opioid, kappa - agonists; Amphetamine derivatives; Agonist; Dopamine; Calcium; Rat; Rodentia; Central nervous system; κ Opioid receptor; Basal ganglion; Corpus striatum; Catecholamine; Glutamate; Vertebrata; Mammalia; Animal; Excitatory aminoacid; Neurotransmitter; Amfetamine; Brain (vertebrata)
• ISSN: 0022-3042; 1471-4159
• DOI: 10.1046/j.1471-4159.1999.0731066.x

The effects of a kappa-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 kappa-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 kappa-opioid receptors suppresses the calcium-dependent component of amphetamine's effects.