Simultaneous real-time correlation of drug effects on dopamine efflux and uptake in rat striatal slices.

Abstract

An increasing body of evidence suggests that striatal dopamine (DA) terminal areas in the rat (the caudate-putamen (CPu) and nucleus accumbens (NAc)) differ in their DA transport sites [ l ] and possibly DA storage pools [2]. We therefore compared the effects of various drugs acting at each site on the efflux and uptake of DA in CPu and NAc. We used fast cyclic voltammetry (FCV) [3] to electrochemically monitor DA efflux and uptake half-life on a sub-second time scale in these two brain areas. The DA uptake blockers GBR 12935 (GBR: 0.2 pM) and bupropion (Bup: 1 pM), the psychomotor stimulant amfonelic acid (AFA: 0.1 pM) and a putative DA mobiliser (the M2 metabolite of nomifensine (M2: 0.5 pM) [4]) were used in order to probe these suggested differences. Their effects on DA efflux and uptake half-life were measured simultaneously at each site. All experiments were conducted in 350 pm brain slices from male Wistar rats (100-1509) superfused with artificial CSF at 32°C. NAc slices were taken at approximately +10.5 mm vs the interaural line [5] and recordings made in the core of the nucleus. CPu slices were taken from approximately +9.2 mm and recordings made from the dorsolateral region. DA efflux was evoked using alternate single pulse ( lp ) and 5 pulse (5p) trains (0.1 ms, 50 Hz, 10 mA, every 10 min) via a bipolar tungsten electrode. FCV was used to monitor DA efflux and subsequent reuptake at a carbon fibre microelectrode sampling at 2 Hz. Drugs were administered after the third 5p stimulation train and were allowed to equilibrate for two hours. DA efflux and uptake half-life after this period was expressed as a percentage of the mean of the pre-drug period. The data on l p stimulations is not reported here. Figure 1 shows the effects of the drugs on DA efflux and uptake half-life in the CPu. It can be seen that M2, GBR and AFA produced significant increases in efflux in the CPu. Only GBR and AFA had a significant effect on uptake half-life.