Adrenergic receptors' responsiveness after acute and chronic treatment with haloperidol in the presence of calcium channel blockade.
The effects of acute and chronic (14 days) treatment with haloperidol (0.5 mg/kg ip) given alone or 15 min after nifedipine (5 mg/kg ip) on responsiveness of the alpha1- and beta-adrenergic receptors was investigated ex vivo by measuring of the second messenger responses. The accumulation of inositol phosphate (IP) or cyclic AMP were measured in brain cortical slices challenged with noradrenaline or isoproterenol. The facilitatory effect of a single dose of haloperidol on IP accumulation (an increase by approximately 50%) was abolished by nifedipine pretreatment. After chronic treatment with haloperidol alone its facilitatory effect disappeared, but a treatment with haloperidol after nifedipine caused a significant increase in IP accumulation. No treatment affected the responses from beta-adrenoceptors. These data show that the action of chronically administered haloperidol may be changed by the concomitant calcium channel blockade that prevents development of adaptation to persistent presence of the drug.
Nalepa
I
I
Institute of Pharmacology, Polish Academy of Sciences, Kraków.
Kreiner
G
G
Kowalska
M
M
Sanak
M
M
Vetulani
J
J
D000316:Adrenergic alpha-Agonists / Q000494:pharmacology; D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D000242:Cyclic AMP / Q000378:metabolism; D018492:Dopamine Antagonists / Q000494:pharmacology*; D006220:Haloperidol / Q000494:pharmacology*; D007295:Inositol Phosphates / Q000378:metabolism; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D009543:Nifedipine / Q000494:pharmacology*; D009638:Norepinephrine / Q000494:pharmacology; D051381:Rats; D018340:Receptors, Adrenergic, alpha-1 / Q000187:drug effects* / Q000378:metabolism; D011943:Receptors, Adrenergic, beta / Q000187:drug effects / Q000378:metabolism
D000316:Adrenergic alpha-Agonists; D000318:Adrenergic beta-Agonists; D002121:Calcium Channel Blockers; D018492:Dopamine Antagonists; D007295:Inositol Phosphates; D018340:Receptors, Adrenergic, alpha-1; D011943:Receptors, Adrenergic, beta; D000242:Cyclic AMP; D009543:Nifedipine; D006220:Haloperidol; D007545:Isoproterenol; D009638:Norepinephrine