Acute depolarization block of A10 dopamine neurons: interactions of morphine with dopamine antagonists.
Extracellular single-unit recording techniques were used to determine the effects of morphine, administered either systematically (intravenous) or locally (microiontophoresis), on ventral tegmental area (A10) dopamine (DA) neuronal activity in animals pretreated with D1 (SCH 23390) or D2 (pimozide) DA receptor antagonists. In rats pretreated with the D2 antagonist pimozide, A10 DA neurons readily entered a state of apparent depolarization block in response to either i.v. or iontophoretically applied morphine. Whether the inactivation of DA neurons was induced by systemic or local morphine, it was reversed in 22 of 27 cases by iontophoretic administration of the inhibitory amino acid transmitter gamma-aminobutyric acid (GABA), suggesting depolarization block as the underlying mechanism. Pretreatment of rats with the D1 antagonist SCH 23390 did not significantly alter the tendency of A10 DA neurons to enter apparent depolarization block in response to morphine. These data support recent behavioral evidence suggesting that the combination of systemic pimozide and ventral tegmental area morphine can result in depolarization inactivation of the mesoaccumbens DA reward system.
Henry
D J
DJ
Wayne State University School of Medicine, Department of Psychiatry, Detroit, MI 48207.
Wise
R A
RA
Rompré
P P
PP
White
F J
FJ
D000704:Analysis of Variance; D000818:Animals; D001552:Benzazepines / Q000494:pharmacology*; D004298:Dopamine / Q000502:physiology*; D018492:Dopamine Antagonists; D004347:Drug Interactions; D004594:Electrophysiology; D007275:Injections, Intravenous; D007478:Iontophoresis; D008297:Male; D009020:Morphine / Q000494:pharmacology*; D009474:Neurons / Q000502:physiology*; D010868:Pimozide / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013681:Tegmentum Mesencephali / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D005680:gamma-Aminobutyric Acid / Q000494:pharmacology
D001552:Benzazepines; D018492:Dopamine Antagonists; D010868:Pimozide; D005680:gamma-Aminobutyric Acid; D009020:Morphine; D004298:Dopamine