The interaction of clonidine with dopamine-dependent behaviour in rodents.
The effect of clonidine on a number of behavioural parameters believed to be expressed through central dopaminergic mechanisms has been studied in rodents. 1. Clonidine (0.06-2 mg/kg) potentiated the circling response to standard doses of both apomorphine (0.25 mg/kg) and amphetamine (3 mg/kg) in mice with unilateral destruction of nigro-neostriatal dopamine nerve terminals. Similarly, clonidine (0.06-2 mg/kg) enhanced the locomotor effect of apomorphine in reserpinised mice. 2. Clonidine (0.5 mg/kg) was without effect on the patterns of stereotypyd behaviours induced by the dopamine agonist apomorphine (0.1-5 mg/kg) in the rat. Unilateral intrastriatal injections of clonidine (5-100 microng) caused no discernable behavioural effects in rats. 3. Injection of apomorphine (10 microng) bilaterally into the region of the nucleus accumbens of the rat resulted in a hyperactive response, while bilateral injection of clonidine (50 microng) into this region caused marked sedation, thus mimicking the effects of these drugs on motor activity when administered systemically. Combinations of systemic or nucleus accumbens apomorphine and clonidine resulted in potentiated stereotype and prolonged hyperactivity responses. 4. Clonidine (0.5 mg/kg) potentiated the cataleptic effect of the dopamine antagonist haloperidol (0.1-2 mg/kg) in rats. Clonidine therefore potentiated those behavioural responses exhibiting a locomotor component (viz. circling and hyperactivity), but was without effect on stereotypy. The potentiation of catalepsy induced by clonidine may be explained in non-specific sedatory terms. It is apparent that clonidine acts through a secondary neurone system which modifies the effects of dopamine receptor stimulation, although the exact site of this interaction is not clear. The tentative conclusion might be that clonidine inhibits 5-HT neuronal activity, and the possible relationships between 5-HT and NA and dopamine are discussed.
D000818:Animals; D001058:Apomorphine / Q000494:pharmacology; D001522:Behavior, Animal / Q000187:drug effects*; D002375:Catalepsy / Q000139:chemically induced; D003000:Clonidine / Q000494:pharmacology*; D003342:Corpus Striatum / Q000187:drug effects; D003913:Dextroamphetamine / Q000494:pharmacology; D004298:Dopamine / Q000378:metabolism*; D004347:Drug Interactions; D006220:Haloperidol / Q000494:pharmacology; D006801:Humans; D008032:Limbic System / Q000187:drug effects; D008297:Male; D051379:Mice; D009043:Motor Activity / Q000187:drug effects; D009638:Norepinephrine / Q000378:metabolism; D051381:Rats; D012110:Reserpine / Q000494:pharmacology; D012701:Serotonin / Q000378:metabolism; D013239:Stereotyped Behavior / Q000187:drug effects
D012701:Serotonin; D012110:Reserpine; D006220:Haloperidol; D003000:Clonidine; D001058:Apomorphine; D003913:Dextroamphetamine; D004298:Dopamine; D009638:Norepinephrine