Differential effects of dopamine D1‐like and D2‐like receptor agonists on water drinking behaviour under thirsty conditions in mice with reduced dopamine secretion

Abstract

The mesolimbic dopamine system is important for reward‐oriented behaviours, such as drinking and eating. However, the precise involvement of dopaminergic neurons and dopamine receptors in water drinking behaviour remains unclear. Here, we generated triple transgenic mice harbouring Slc6a3(DAT)‐icre/ERT2, Camk2a‐loxP‐STOP‐loxP‐tetracycline transactivator and tetO‐tetanus toxin constructs, in which the release of dopamine is blocked by tetanus toxin. These mice, referred to as dopamine secretion interference mice, had reduced dopamine secretion in the striatum (61.4%) and the nucleus accumbens (54.5%). They showed adequate limb strength and food consumption, similarly to control mice, but exhibited motor control impairment in a challenging rotarod test. Dopamine secretion interference mice made fewer licks and had fewer bursts than control mice during a licking test under thirsty conditions. To elucidate the influence of dopamine receptors in the altered drinking behaviour, a dopamine D1 or D2/D3 receptor agonist (A68930 or ropinirole, respectively) was administered prior to the licking microstructure analysis. Treatment with the D1 agonist restored the total number of licks but not the burst number in dopamine secretion interference mice. By contrast, the D2/3 agonist impeded water drinking behaviour in both transgenic and control mice. The present findings indicate that D1 receptor activation partially ameliorates the altered drinking behaviour of the dopamine secretion interference mice and suggest that D1 receptor activity impacts drinking under thirsty conditions.

Pairing Binge Drinking and a High-Fat Diet in Adolescence Modulates the Inflammatory Effects of Subsequent Alcohol Consumption in Mice

“…Furthermore, the hypothalamic and endocrine signals can decrease the activity of the dopaminergic system [ 92 ]. However, another possible explanation of these results is that long-term HFD consumption caused a general attenuation of dopamine signaling that may result in reduced alcohol drinking [ 93 , 94 , 95 ]. Exposure to HFD reduces dopamine receptor D2 protein expression levels in the striatum and leads to changes in dopamine synthesis and uptake [ 96 , 97 , 98 , 99 ].…”