Effect of alpha-adrenoreceptors in the control of spontaneous motility and morphine withdrawal syndrome.
The effects of different alpha-2 agonists on the spontaneous motility in naive and morphine tolerant mice were studied. Clonidine caused a reduction at the lower (1-3 micrograms Kg-1 i.p.) and higher (100 micrograms Kg-1 i.p.) doses and no effect at 10-30 micrograms Kg-1 i.p. in naive mice, while an increase was found at the intermediate doses (10-30 micrograms Kg-1 i.p.) in morphine tolerant mice. The clonidine-induced inhibition on spontaneous motility at the lower and higher doses was prevented both in naive and tolerant mice by idazoxan pretreatment. In morphine-treated animals the increase induced by clonidine was antagonized by prazosin. The action of guanabenz and guanfacine on locomotion differed from clonidine, by producing inhibition only at higher doses (100-300 micrograms Kg-1 i.p.). Clonidine, but not guanfacine or guanabenz, prevented the withdrawal syndrome precipitated by naloxone. Thus the only alpha-2 agonistic properties do not appear sufficient to explain the prevention of morphine abstinence by clonidine in mice, which can represent a single model to screen anti-withdrawal drugs.
Antonelli
T
T
Istituto di Farmacologia, Università di Ferrara.
Morari
M
M
Magri
A
A
Bianchi
C
C
D000316:Adrenergic alpha-Agonists / Q000494:pharmacology / Q000627:therapeutic use*; D000818:Animals; D003000:Clonidine / Q000494:pharmacology / Q000627:therapeutic use; D004146:Dioxanes / Q000494:pharmacology; D004361:Drug Tolerance; D006143:Guanabenz / Q000494:pharmacology / Q000627:therapeutic use; D016316:Guanfacine / Q000494:pharmacology / Q000627:therapeutic use; D019329:Idazoxan; D051379:Mice; D009020:Morphine / Q000633:toxicity*; D009043:Motor Activity / Q000187:drug effects*; D009270:Naloxone / Q000494:pharmacology; D011224:Prazosin / Q000494:pharmacology; D011942:Receptors, Adrenergic, alpha / Q000502:physiology*; D013375:Substance Withdrawal Syndrome / Q000188:drug therapy* / Q000503:physiopathology
D000316:Adrenergic alpha-Agonists; D004146:Dioxanes; D011942:Receptors, Adrenergic, alpha; D016316:Guanfacine; D009270:Naloxone; D009020:Morphine; D006143:Guanabenz; D003000:Clonidine; D011224:Prazosin; D019329:Idazoxan