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R Kuczenski

Publications and source records attributed to R Kuczenski.

88 records · Page 5Linked to original sources
PubMed1977

Amphetamine-haloperidol interactions in rat striatum: failure to correlate behavioral effects with dopaminergic and cholinergic dynamics.

Previous reports have suggested that the hyperactivity and stereotypy produced by amphetamine (AMP) and the catalepsy produced by haloperidol (HAL) are mediated by striatal dopaminergic mechanisms. In the present study, we have measured the behavioral effects of AMP and HAL, and their effects on striatal dopaminergic function, using both an index of pre-synaptic activity (synaptosomal dopamine (DA) synthesis) and a parameter which we suggest will reflect post-synaptic dopaminergic function (sodium-dependent, high affinity choline uptake). Administration of 2 mg/kg AMP produces hyperactivity and causes a decrease in DA biosynthesis, both of which are blocked by 0.75 mg/kg HAL. AMP (5 mg/kg) produces stereotypy, further decreases DA biosynthesis and causes a decrease in choline uptake, consistent with stimulation of DA receptors. However, while pretreatment with 3 mg/kg HAL completely blocked the stereotypy induced by 5 mg/kg AMP it failed to reverse the effects of this dose on either DA biosynthesis or choline uptake. These data suggest that either 5 mg/kg AMP affects straital dopaminergic and cholinergic parameters by a mechanism independent of HAL sensitive receptors, or the stereotypy produced by high doses of AMP are not related to striatal dopaminergic and cholinergic function.

Amphetamine↗
PubMed1977

Differential effects of reserpine and tetrabenazine on rat striatal synaptosomal dopamine biosynthesis and synaptosomal dopamine pools.

Rat striatal dopamine (DA) levels and synaptosomal DA synthesis were determined after the administration of the catecholamine-depleting agents reserpine (RES) and tetrabenazine (TBZ). Striatal synaptosomal DA synthesis remained unchanged from control levels after Res administration over a wide range of doses (0.5-5 mg/kg) and times (up to 48 hour). In contrast, after TBZ administration, DA synthesis rapidly increased to values greater than 200% of control values, then returned to control levels. The changes in DA synthesis inversely paralleled the depletion of and recovery of striatal DA levels. The increased levels of DA synthesis did not appear to originate with alterations either in the kinetic properties of tyrosine hydroxylase or in the availability of exogenous or endogenous tyrosine. To assess the contribution of synaptosomal DA pools to the regulation of DA synthesis in tissue preparations from RES-or TBZ-pretreated animals, synaptosomal DA synthesis was assessed in the presence of DA releasing agents and compared with analogous experimental manipulations on tissue preparations from animals pretreated with alpha-methyltyrosine or the monoamine oxidase inhibitor, clorgyline. The data are consistent with a differential in vivo interaction of RES and TBZ with a nerve ending pool of DA which participates in end-product inhibition of tyrosine hydroxylase.

Animals↗
PubMed1975

Differential effects of D- and L-amphetamine and methylphenidate on rat striatal dopamine biosynthesis.

Methylphenidate and the optical isomers of amphetamine have differential effects, in vivo and in vitro on rat striatal synaptosomal dopamine (DA) biosynthesis. Whereas the systemic administration of D- or L-amphetamine produces a dose-dependent decrease in synaptosomal DA synthesis, with ED50's of 1.1 and 3.5 mg/kg, respectively, methylphenidate, at doses which produce comparable degrees of stereotypes behavior, has no effect on this measure of DA biosynthesis. In vitro, D- and L-amphetamine exhibit a three-fold difference in ED50's (1 times 10-minus 6 M and 3 times 10-minus 6 M, respectively) with respect to both activation of striatal synpatosomal DA synthesis, and to reversal of reserpine-induced inhibition of DA synthesis. In contrast, although in vitro methylphenidate can partially activate DA synthesis, it does not overcome the reserpeine-induced inhibition. The data are discussed in terms of the possible differential mechanisms by which these two types of stimulants may exert their effects on sterotypy.

Amphetamine↗