Elsevier

Neuroscience

Volume 88, Issue 3, February 1999, Pages 837-845
Neuroscience

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

https://doi.org/10.1016/S0306-4522(98)00264-4Get rights and content

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.

Section snippets

Animals

Male hooded Lister rats (Bantin and Kingman, U.K.) were used throughout, of body weights between 200 and 270 g. Prior to slice preparation, the rats were housed, four per cage, at 21±1°C, with 55±10% relative humidity, and free access to tap water and laboratory rodent chow (CRM). Lighting was on a 12 h light/dark cycle, with the light phase between 09.00 to 21.00 and slices were prepared each day between 09.00 and 10.00.

Preparation of ventral tegmental area slices for electrophysiological recordings

The animals were killed by cervical dislocation. The skull was opened from

Effects of corticosterone on spontaneous firing and responses to dopamine

Corticosterone had no effect, at any of the concentrations (50 nM to 2 μM), on the spontaneous firing of dopamine-sensitive cells in the VTA (Fig. 1). The depression of firing rate produced by application of dopamine, 5 μM or 15 μM was also unaltered, by any of the corticosterone concentrations used.

Effects of corticosterone on the responses to excitatory amino acids

Corticosterone, at concentrations of 100 nM to 1 μM, significantly increased the responses to NMDA (Fig. 2a and b). The effects was seen with both concentrations of NMDA, 5 μM and 15 μM. No significant

Discussion

The results in this study demonstrated that corticosterone, at concentrations of 100 nM and above, potentiated the responses of VTA neurons to excitatory amino acids. These effects were quite specific, as no changes were seen in spontaneous firing or in the inhibitory effect of dopamine. The mineralocorticoid, aldosterone, did not show any potentiation of the responses to NMDA, while the glucocorticoid (Type II) receptor antagonist, RU38486, prevented the effect of corticosterone on the response

Conclusion

Effects such as we have reported here, of corticosterone on VTA neurons, could mediate the effects of stress in causing sensitization to drugs of abuse. The NMDA subtype of receptor is known to be involved in the development of sensitization. NMDA antagonists prevent the development of sensitization to amphetamine, cocaine and nicotine.13, 33The effect on amphetamine sensitization has been found to be produced by administration of an NMDA antagonist directly into the VTA,[13]providing good

Unlinked References

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Acknowledgements

This work received financial support from the Medical Research Council, U.K.

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