Chemogenetic inhibition of dopaminergic projections to the nucleus accumbens has sexually dimorphic effects in the rat gambling task.

Behavioral Neuroscience
Tristan J HynesCatharine A Winstanley

Abstract

Women and men can differ in their propensity to take risks and develop impulse control and addiction disorders. Sexual dimorphisms in behavioral control by the mesolimbic dopaminergic reward system may underlie these phenomena, given its sensitivity to gonadal hormones. However, this is hard to test experimentally using humans. Using the rat gambling task (rGT), we investigated what impact acute inhibition of accumbal dopamine had on decision-making and impulsivity in animals of both sexes. We expressed an inhibitory designer receptor exclusively activated by designer drugs (hM4D[Gi]) in the accumbal dopaminergic efferents of female and male transgenic (Tg) rats, engineered to selectively express cre recombinase in neurons synthesizing tyrosine hydroxylase. We then trained the rats to perform the rGT and assessed the effect of an acute clozapine-n-oxide (0-3 mg/kg) challenge. Chemogenetic inhibition of dopaminergic projections to the accumbens did not affect choice in females, perhaps due to low levels of risky choice in Tg+ animals at baseline, but induced a switch from risky to optimal decision-making in males performing the cued rGT. This manipulation also decreased motor impulsivity but only in females. These data support t...Continue Reading

Citations

Feb 10, 2021·Addiction Biology·Tristan J HynesCatharine A Winstanley
Mar 3, 2021·Psychopharmacology·Chloe S ChernoffCatharine A Winstanley
Jul 5, 2021·Progress in Neuro-psychopharmacology & Biological Psychiatry·Claire J FoldiBrian J Oldfield

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