Resistance to extrapyramidal effects of opiates in rats chronically treated with SCH 23390.
Rats made tolerant to morphine show neither a change in brain opiate receptor number nor altered sensitivity to the inhibitory effect of opiates on striatal adenylate cyclase (AC) activity. Interestingly, SCH 23390, a selective blocker of D1 dopamine (DA) receptors which, given chronically to rats, induces a 32% increase in D1 receptor number and increases the Vmax of D1-stimulated striatal AC, resulted in marked resistance to acute morphine effects. In particular, rats chronically treated with SCH 23390 failed to show muscular rigidity and increased striatal dihydroxyphenylacetic acid (DOPAC) concentration after morphine. Moreover, basal striatal AC activity in these animals had a significantly reduced sensitivity to opiate inhibition. On the other hand, decreased AC sensitivity to acetylcholine (ACh) inhibition observed in the striatum of rats chronically treated with DFP, an irreversible blocker of acetylcholinesterase, appeared to be secondary to the downregulation of muscarinic receptors and thus did not modify the opiate inhibitory capacity. It was concluded that although a potentiation of striatal AC impairs opiate action, such mechanism is not involved in morphine tolerance.
De Montis
G M
GM
Institute of Pharmacology and Biochemical Pathology, University of Cagliari, Italy.
Devoto
P
P
Meloni
D
D
Porcella
A
A
Saba
P
P
Tagliamonte
A
A
D015102:3,4-Dihydroxyphenylacetic Acid / Q000378:metabolism; D000818:Animals; D001552:Benzazepines / Q000494:pharmacology*; D002375:Catalepsy / Q000139:chemically induced; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism*; D004361:Drug Tolerance; D008297:Male; D009020:Morphine / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D011954:Receptors, Dopamine / Q000378:metabolism*; D017447:Receptors, Dopamine D1
D001552:Benzazepines; D011954:Receptors, Dopamine; D017447:Receptors, Dopamine D1; D015102:3,4-Dihydroxyphenylacetic Acid; D009020:Morphine