Molecular mechanisms in the actions of morphine and viminol (R2) on rat striatum.
Analgesic doses of morphine and viminol R2 increase the turnover rate of dopamine (DA) in rat striatum but fail to increase the striatal concentration of adenosine 3',5'-monophosphate (cAMP) or the affinity of tyrosine hydroxylase (TH) for the pteridine cofactor. When morphine is added to striatal homogenates, it changes neither the basal activity of adenylate cyclase nor the enzyme activation by DA. Similarly to morphine, haloperidol enhances the turnover rate of striatal DA, but unlike morphine it increases the affinity of TH for the pteridine cofactor and blocks the in vitro activation of striatal adenylacte cyclase by DA. Morphine (52 mumol/kg i.p.), viminol R2 (7 mumol/kg i.p.) or haloperidol (2.6 mumol/kg i.p.) fails to increase the striatal cAMP contrations. However (+)-amphetamine (4.8 mumol/kg i.p.) increases DA turnover rate and the striatal cAMP content, but, in doses up to 12.8 mumol/kg i.p., it fails to change the affinity of TH for the pteridine cofactor. This study shows that although (+)-amphetamine, haloperidol and morphine increase the turnover rate of striatal DA each drug possesses a specific profile in its action on molecular mechanisms that control the function of striatal dopaminergic synapses.
D000818:Animals; D001058:Apomorphine / Q000494:pharmacology; D002395:Catecholamines / Q000378:metabolism; D003342:Corpus Striatum / Q000032:analysis / Q000187:drug effects* / Q000201:enzymology; D000242:Cyclic AMP / Q000032:analysis; D003913:Dextroamphetamine / Q000494:pharmacology; D004298:Dopamine / Q000378:metabolism; D004983:Ethanolamines / Q000494:pharmacology*; D006220:Haloperidol / Q000494:pharmacology; D007700:Kinetics; D008297:Male; D009020:Morphine / Q000494:pharmacology*; D051381:Rats; D011955:Receptors, Drug; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism
D002395:Catecholamines; D004983:Ethanolamines; D011955:Receptors, Drug; D009020:Morphine; D000242:Cyclic AMP; D014446:Tyrosine 3-Monooxygenase; D006220:Haloperidol; D001058:Apomorphine; D003913:Dextroamphetamine; D004298:Dopamine