Evidence that noradrenaline modulates the increase in striatal dopamine metabolism induced by muscarinic receptor stimulation

The effect of oxotremorine was studied on the concentration of homovanillic acid (HVA) and 3-methoxy-4-hydroxyphenylethylglycol (MHPG) in the corpus striatum of rats. At a dose of 1 mg/kg oxotremorine incresed HVA levels by 68% and MHPG, by 51%. MHPG was also increased in the nucl. accumbens (58%) and neocortex (42%). Pretreatment with clonidine 0.1 mg/kg, abolished the increased in MHPGin the striatum and significantly inhibited the rise in HVA. 1-Propanolol 2.5 mg/kg, but not d-propanolol, had an effect similar to that of clonidine. A lower dose of oxotremorine (0.5 mg/kg) increased striatal HVA by 36% but did not alter MHPG levels This increase in HVA was not reduced by 1-propranolol. Eight days after bilateral lesions of the locu coeruleus, there was a reduction in the basal concentrations of noradrenaline (41%) and MHPG (57%) in the striatum. The data suggest that a higher doses of oxotremorine (1 mg/kg), but not a lower dose (0.5 mg/kg), a noradrenergic pathway is stimulated to increase the rate of metabolism of noradrenaline in the striatum. Oxotrremorine also appears to increase dopamine metabolism in the striatum by at least two separate mechanisms, one of which involves the mediation of noradrenaline.