Abstract

The experiments described in the present thesis address the specific role of dopamine (DA) tone in brain stimulation reward (BSR). The level of extracellular dopamine in the rat nucleus accumbens was measured by means of in-vivo microdialysis in rats receiving electrical stimulation of the medial forebrain bundle. The first experiments characterize changes in DA tone as a function of reward predictability and duty cycle under circumstances in which phasic release of DA, as measured by fast-scan cyclic voltammetry, has been reported to be absent (Garris et al., 1999). The results obtained using several different reinforcement schedules suggest that DA tone reflects the duty cycle of the stimulation rather than the predictability of the reward. In contrast to the transient elevation observed when stimulation is delivered at short (1.5 s) inter-train intervals, stimulation trains separated by long (12 s) inter-train intervals can sustain a stable level of DA tone for up to two hours. This difference in the stability of DA tone has repercussions for the behaviour sustained by BSR, as measured by means of the curve-shift paradigm. When DA tone was measured under similar circumstances to those in the Garris et al. (1999) study, a robust increase in tonic DA release was observed, on each schedule tested, in sharp contrast to the transient changes in phasic DA release described by Garris et al. (1999). These results suggest that phasic and tonic DA release are under differential control. In an additional experiment, the reinforcement-mountain model and testing paradigm were used to determine the stage(s) of processing at which DA tone influences the pursuit of BSR. The mountain model relates pursuit of BSR to the cost and strength of the electrical stimulation. DA reuptake was blocked by continuous subcutaneous infusion of cocaine in a novel manner that avoids tissue damage. The 3D structure defined by time-allocation, reward cost and reward strength. always shifted rightward along the cost axis but rarely along the strength axis. This result implies that the leftward shifts seen in "rate-frequency" studies of the effect of cocaine on intracranial self-stimulation (ICSS) are misleading: these effects are due to displacement of the diagonally oriented face of the 3D structure along the cost axis. The results demonstrate that DA tone exerts its influence at a later processing stage than originally proposed and long believed.