PEMOLINE ALTERS DOPAMINE MODULATION OF SYNAPTIC RESPONSES OF NEOSTRIATAL NEURONS IN-VITRO

Pemoline, a central stimulant, administered systemically at high doses (300 mg/kg) reliably produces self-biting behavior in rats. Pemoline- induced self-biting shares many similarities with self-injury seen in certain human disorders. Recent evidence has shown that alterations in neostriatal neurochemistry accompany the self-biting behavior seen in the rat. The present study used intracellular electrophysiological te chniques to reveal changes in neostriatal cellular physiology in slice s from rats which had displayed self-injury. Depolarizing postsynaptic potentials (DPSPs) were examined in neostriatal slices from rats that received pemoline and had been engaging in self-injurious behavior an d from two control populations: rats that received the same concentrat ion of pemoline and did not engage in self-biting, and rats that recei ved vehicle alone (peanut oil). Data were acquired in standard artific ial cerebral spinal fluid. DPSPs were evoked by cortical electrical st imulation in the slice. In neurons from rats that received the vehicle or that had received pemoline but had not engaged in self-injury, dop amine (DA, 20 mu M) application produced a significant decrease in the size of the cortically evoked neostriatal DPSP. In contrast, DA appli cation produced an increase in DPSP size in neurons from rats which ha d received pemoline and had engaged in self-injury. Bath application o f a combination of D-1 and D-2 receptor agonists best replicated the e nhancing effect of DA. Furthermore, the enhancement could be blocked b y pretreatment with the competitive N-methyl-d-aspartate receptor anta gonist, 2-amino-5-phosphonopentanoic acid. The results indicate that a lterations in neostriatal DA-glutamate interactions accompany pemoline injections which produce self-injurious behavior.