Effects of corticosterone on excitatory amino acid responses in dopamine-sensitive neurons in the ventral tegmental area

Abstract

The ventral tegmental area is involved in reward processes and in drug dependence and sends dopaminergic projections to the nucleus accumbens and prefrontal cortex. Stress, and glucocorticoid hormones, are thought to play an important role in the development of drug dependence, but there has been little investigation of the effects of these hormones on ventral tegmental function. The present study examined the effects of corticosterone on single-unit recordings from dopamine-sensitive neurons in the ventral tegmental area in midbrain slices. At concentrations of 100 nM and above, corticosterone potentiated the responses to N-methyl- d-aspartate. This effect was not seen when the calcium concentration of the bathing medium was reduced to 0.1 mM. Responses to α-amino-3-hydroxy-5-methylisoxazole-4-propionate and kainic acid were also considerably potentiated, at concentrations of corticosterone over 100 nM, while there was some evidence of decreases in these responses at the 100 nM concentration of this hormone. Aldosterone, at concentrations of 100 nM and above reduced the responses to N-methyl- d-aspartate, but had no effects at lower concentrations. RU38486, which acts as an antagonist at glucocorticoid (Type II) receptors, prevented the effects of corticosterone on responses to N-methyl- d-aspartate, with no effect on the spontaneous firing rate or on the effects of N-methyl- d-aspartate in the absence of corticosterone. The latter result, and the effects of aldosterone, suggest that the potentiation of responses to N-methyl- d-aspartate was mediated through Type II glucocorticoid receptors. This study suggests that potentiation of responses to excitatory amino acids by corticosterone may alter the function of ventral tegmental neurons during stress, and it is possible that this effect is involved in the development of drug dependence.