MK-801 INCREASES LOCOMOTOR-ACTIVITY WITHOUT ELEVATING EXTRACELLULAR DOPAMINE LEVELS IN THE NUCLEUS-ACCUMBENS

In vivo microdialysis was used in freely moving rats to determine whet her the locomotor stimulant effects of dizocilpine maleate (MK-801) we re related to increased dopamine (DA) release within the nucleus accum bens (N. Ace.). Each experiment began with a baseline period of at lea st 2 h (starting 15-20 h after insertion of concentric, removable dial ysis probes), during which activity records and dialysate samples were collected every 20 min. Rats in the first experiment then were inject ed with MK-801 (0.125, 0.25, or 0.50 mg/kg, i.p.) or saline, and activ ity and extracellular levels of DA, dihydroxyphenylacetic acid (DOPAC) , and homovanillic acid (HVA) were measured for a further 160 min post -injection. In a second experiment, rats were given 1.5 mg/kg d-amphet amine sulphate 40 min after receiving the same doses of MK-801, and te sting was continued for 120 min. Rats in a third experiment were given low, autoreceptor-preferring doses of apomorphine hydrochloride (25 o r 50 mu g/kg, s.c.) or its vehicle 40 min after injection of 0.25 mg/k g MK-801 and then monitored for 120 min. MK-801 produced strong and co nsistent increases in locomotor activity that were augmented by amphet amine and greatly reduced by the low doses of apomorphine. MK-801 did not increase extracellular DA levels within the N. Ace. when given alo ne, and it failed to influence the changes in extracellular DA produce d by d-amphetamine and apomorphine. MK-801 did produce consistent, dos e-related increases in DOPAC and HVA that were probably not related to transmitter release. These results indicate that the increases in loc omotor activity seen following MK-801 do not arise from a drug-induced increase in DA levels within the N. Ace. (C) 1996 Wiley-Liss, Inc.