Effect of long-term rolipram administration on the sensitivity of alpha 2-adrenoceptors in rat brain.
The effects of single and chronic doses of rolipram on the sensitivity of alpha 2-adrenoceptors have been compared with the phosphodiesterase inhibitors, isobutylmethylxanthine (IBMX) and ICI 63,197, and the antidepressant, desipramine. While pretreatment with a single dose of rolipram, ICI 63,197 or IBMX administered either 1 or 24 h prior to clonidine (0.1 mg/kg) enhanced clonidine-induced hypothermia and hypoactivity, chronic dosing (twice daily for 14 days) with desipramine (10 mg/kg) or rolipram (5 mg/kg) antagonized these behavioural effects. In contrast, chronic dosing with IBMX or ICI 63,197 failed to antagonize clonidine-induced hypothermia and hypoactivity. In binding studies neither ICI 63,197, IBMX, rolipram nor desipramine induced changes in the binding of 3H-labelled clonidine to rat cerebral cortical membranes following chronic administration. The failure of ICI 63,107 and IBMX to antagonize clonidine-induced hypothermia and hypoactivity suggests that the antidepressant effect of rolipram is independent of its phosphodiesterase inhibitor property.
Mustafa
M R
MR
Welsh School of Pharmacy, UWIST, Cardiff, U.K.
Stolz
J F
JF
Luscombe
D K
DK
D015056:1-Methyl-3-isobutylxanthine / Q000008:administration & dosage / Q000494:pharmacology; D000818:Animals; D001921:Brain / Q000187:drug effects*; D003000:Clonidine / Q000378:metabolism / Q000494:pharmacology; D003891:Desipramine / Q000008:administration & dosage / Q000494:pharmacology; D004334:Drug Administration Schedule; D008124:Locomotion / Q000187:drug effects; D008297:Male; D010726:Phosphodiesterase Inhibitors / Q000008:administration & dosage / Q000494:pharmacology*; D011743:Pyrimidines / Q000008:administration & dosage / Q000494:pharmacology; D011760:Pyrrolidinones / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects* / Q000502:physiology; D020889:Rolipram
D010726:Phosphodiesterase Inhibitors; D011743:Pyrimidines; D011760:Pyrrolidinones; D011942:Receptors, Adrenergic, alpha; C006313:ICI 63197; D020889:Rolipram; D003000:Clonidine; D015056:1-Methyl-3-isobutylxanthine; D003891:Desipramine