Effects of EEDQ on the synthesis and metabolism of dopamine in preweanling and adult rats.

Ontogenetic differences in dopamine (DA) synthesis and metabolism were assessed in 17- and 90-day-old rats injected i.p. with the alkylating agent N-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline (EEDQ) 24 hr prior to sacrifice. DA synthesis was determined by measuring DOPA accumulation after NSD-1015 induced inhibition of DOPA decarboxylase; whereas, DA turnover was estimated by measuring DA accumulation and DOPAC efflux after pargyline induced inhibition of monoamine oxidase. In addition, some of the rats were pretreated with the competitive D1 and D2 antagonists SCH 23390 (1.0 mg/kg) and sulpiride (100 mg/kg) in order to protect these receptor subtypes from EEDQ-induced inactivation. The latter procedure was used to determine whether EEDQ's presynaptic effects were mediated by D1 and D2 receptors or were nonspecific. The results showed that 7.5 mg/kg EEDQ increased the striatal DA synthesis of both preweanling and adult rats: effects eliminated if D1 and D2 receptors were protected by pretreatment with SCH 23390 and sulpiride. Striatal DA levels of both age groups were depressed by EEDQ treatment, while DA accumulation was unaffected. Age-dependent effects were apparent however, as 7.5 mg/kg EEDQ increased the DOPAC turnover of adult, but not 17-day-old rats. The inability of EEDQ to affect the DOPAC turnover of the younger rats was apparently not dose related, as 15 mg/kg EEDQ did not affect the striatal DOPAC turnover of 17-day-olds. In adult rats, the EEDQ-induced increase in DOPAC turnover was not mediated by DA receptors, as pretreatment with SCH 23390 and sulpiride did not block EEDQ's effects.(ABSTRACT TRUNCATED AT 250 WORDS)