Stereospecific effects of ketamine on dopamine efflux and uptake in the rat nucleus accumbens

In addition to being a general anaesthetic, ketamine is a recognized drug o f abuse. Many, if not all, drugs of abuse have been shown to increase dopam ine efflux in the nucleus accumbens (NAc). As ketamine is optically active, we examined if its actions on dopamine efflux in the NAc were stereoselect ive. Slices of rat NAc were superfused with artificial CSF at 32 degrees C. Dopamine efflux was evoked by electrical stimulation (1 or 20 pulses, 100 Hz) and measured using fast cyclic voltammetry. (+/-)-Ketamine 100 mu mol l itre(-1) increased dopamine efflux (to mean 174 (SEM 17)% Of control, P<0.0 5) and slowed dopamine uptake half-time (T-1/2) to 164 (17)% of control, as did (+)-ketamine 100 mu mol litre(-1) (efflux 236 (16)% (P<0.001); uptake T-1/2 177 (25)% (P<0.05)). The (-)-isomer was inactive. The effect of (+)-k etamine on dopamine efflux did not correlate with its action on dopamine up take. (+)-Ketamine increased dopamine efflux on single pulse stimulation bu t to a lesser extent than on 20 pulse trains (P<0.05). (+)-Ketamine was una ble to block the inhibitory effect of quinpirole on single pulse dopamine e fflux. Neither MK 801 10 mu mol litre(-1) nor metoclopramide 1 mu mol litre (-1) had any effect on dopamine release after short train stimuli (20 pulse s, 100 Hz). We conclude that the (+)-isomer is the active form of ketamine and increases NAc dopamine efflux not by block of dopamine uptake, autorece ptors or NMDA receptors, but by mobilization of the dopamine storage pool t o releasable sites.