Quinine and 4-aminopyridine inhibit the stimulatory output of dopamine in nucleus accumbens and the behavioural activity produced by morphine.
We have tested the effects in rats of two potassium channel blocking drugs, 4-aminopyridine and quinine, on morphine-induced stimulation of behavioural activity and on dopamine outflow in nucleus accumbens using microdialysis. Morphine (1 mg/kg s.c.) increased dopamine output by 123% in nucleus accumbens. This dose of morphine also stimulated behavioural activity which in the early part of the time course corresponded closely with the increase of dopamine outflow in nucleus accumbens. Both of these effects were maximal 60-80 min after the morphine administration. 4-Aminopyridine (1 mg/kg i.p.) or quinine (50 mg/kg i.p.) injected 20 min before morphine inhibited the maximal effect on dopamine output by 88 and 80% respectively. Pretreatment with the two potassium channel blocking drugs also resulted in a reduction of morphine-induced stimulation of behavioural activity, 4-aminopyridine by 77% and quinine by 66%. In summary this study demonstrates that two drugs known to block potassium channels inhibit two effects of morphine associated with mesolimbic dopamine function.
Pei
Q
Q
Oxford University SmithKline Beecham Centre for Applied Neuropsychobiology, University Department of Clinical Pharmacology, Radcliffe Infirmary, UK.
Elliott
J M
JM
Grahame-Smith
D G
DG
Zetterström
T
T
D015761:4-Aminopyridine / Q000494:pharmacology*; D000700:Analgesics / Q000494:pharmacology; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D004298:Dopamine / Q000378:metabolism*; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; D004745:Enkephalins / Q000494:pharmacology; D066298:In Vitro Techniques; D008297:Male; D017551:Microdialysis; D009020:Morphine / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D009714:Nucleus Accumbens / Q000187:drug effects / Q000378:metabolism*; D015221:Potassium Channels / Q000187:drug effects; D011803:Quinine / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley
D000700:Analgesics; D004745:Enkephalins; D015221:Potassium Channels; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; D009020:Morphine; D011803:Quinine; D015761:4-Aminopyridine; D004298:Dopamine