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 techniques to reveal changes in neostriatal cellular physiology in slices 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 and from two control populations: rats that received the same concentration of pemoline and did not engage in self-biting, and rats that received vehicle alone (peanut oil). Data were acquired in standard artificial cerebral spinal fluid. DPSPs were evoked by cortical electrical stimulation in the slice. In neurons from rats that received the vehicle or that had received pemoline but had not engaged in self-injury, dopamine (DA, 20 microM) application produced a significant decrease in the size of the cortically evoked neostriatal DPSP. In contrast, DA application produced an increase in DPSP size in neurons from rats which had received pemoline and had engaged in self-injury. Bath application of a combination of D1 and D2 receptor agonists best replicated the enhancing effect of DA. Furthermore, the enhancement could be blocked by pretreatment with the competitive N-methyl-d-aspartate receptor antagonist, 2-amino-5-phosphonopentanoic acid. The results indicate that alterations in neostriatal DA-glutamate interactions accompany pemoline injections which produce self-injurious behavior.