Specific inhibition of hypothalamic self-stimulation by selective reuptake blockade of either 5-hydroxytryptamine or noradrenaline.

The effects of two new phthalane-derived bicyclic thymoleptics on hypothalamic self-stimulation were investigated in rats. The drugs, LU 10-171 and LU 5-003 are potent and highly selective reuptake blockers of 5-hydroxytryptamine (5-HT) and noradrenaline (NA), respectively. The use of a two-way shuttle-box permitted the differentiation of specific reward modulation effects from the variety of non-specific performance changes that these drugs may produce. Selective reuptake blockade of either 5HT or NA produced a dose-dependent reduction in reward that could be clearly dissociated from any non-specific performance decrements. Besides providing direct evidence for a significant role for 5HT in the mediation of hypothalamic self-stimulation, these data show that symphy increasing transmitter availability is not a sufficient condition to enhance self-stimulation reward. It is suggested that self-stimulation is dependent on response-contingent transmitter release and that any operation that increases reward-transmitter availability in a response-independent manner should attenuate self-stimulation.