DOPAMINERGIC AGONISTS ADMINISTERED INTO THE NUCLEUS-ACCUMBENS - EFFECTS ON EXTRACELLULAR GLUTAMATE AND ON LOCOMOTOR-ACTIVITY

The hypothesis to be tested was that increased dopaminergic transmissi on induced by amphetamine in the nucleus accumbens results in increase d glutamatergic neurotransmission in this brain area and that the incr ease in level of this neurotransmitter contributes to behavioral effec ts of psychostimulant drugs. Amphetamine (1 mg/kg, i.p.) increased the amount of extracellular glutamate in the accumbens, as measured by in vivo dialysis, and stimulated locomotor activity. Amphetamine (10 mM) infused into the accumbens by reverse dialysis through the probe prod uced a similar stimulation of locomotor activity as systemic amphetami ne but a greater increase in extracellular glutamate levels. Both of t hese responses to amphetamine were attenuated by either the selective D1 antagonist SCH23390 or the selective D2 antagonist eticlopride. The combination of a D1 and D2 agonist, SKF38393 (20 mM) and quinpirole ( 50 mM), administered into the accumbens by reverse dialysis also incre ased extracellular glutamate and stimulated locomotor activity. Admini stration of a glutamate uptake inhibitor, threo-beta-hydroxy-aspartate (50 mM), increased extracellular glutamate but did not stimulate loco motor activity. Systemic administration of caffeine (15 mg/kg, i.p.) i ncreased locomotor activity but did not increase extracellular levels of glutamate. These data suggest that activation of dopaminergic recep tors in the nucleus accumbens results in stimulation of locomotor acti vity and in activation of glutamatergic transmission in this brain reg ion. However, an increase in glutamate levels in the nucleus accumbens is neither sufficient nor necessary to produce a stimulation of locom otor activity. (C) 1998 Elsevier Science B.V.