THE ROLE OF DOPAMINE AND AMPA KAINATE RECEPTORS IN THE NUCLEUS-ACCUMBENS IN THE HYPERMOTILITY RESPONSE TO MK801

The purpose of this study was to evaluate the role of endogenous dopamine in the hypermotility response to MK801. The administration of MK801 (0.1 mg/kg, SC) to rats produced an intense stimulation of coordinated locomotor activity, which was not associated with stereotyped behavior. This stimulatory response was inhibited by pretreatment with either reserpine (5 mg/kg, IP) or alpha-methyl-p-tyrosine (2 doses of 250 mg/kg, IP). Similarly, pretreatment with the D2 antagonist eticlopride (0.03 mg/kg, SC) or the D1 antagonist SCH23390 (0.1 mg/kg, SC) produced a marked inhibition of MK801-stimulated hypermotility, and the combination of eticlopride (0.03 mg/kg, SC) and SCH23390 (0.03 mg/kg, SC) produced a greater inhibition of MK801-stimulated locomotion than either agent alone. The administration of SCH23390 or eticlopride directly into the nucleus accumbens inhibited the locomotor response to MK801, with the combination of both drugs producing a greater inhibition than either agent alone. The intra-accumbens administration of the alpha-amino-3-hydroxy-5-methylisoxazole-4-propionate (AMPA)/kainate receptor antagonists DNQX or GAMS also inhibited the locomotor response produced by MK801. These data suggest that the activation of D1 and D2 dopaminergic receptors and AMPA/kainate excitatory amino acid receptors in the nucleus accumbens is required for the stimulation of locomotor activity produced by MK801.