Dopamine D2 receptor stimulation inhibits cold-initiated thermogenesis in brown adipose tissue in conscious rats

Abstract

Dopamine D2-like receptor agonists cause hypothermia. We investigated whether inhibiting heat production by interscapular brown adipose tissue (iBAT), a major thermogenic organ in rats, contributes to hypothermia caused by dopamine D2-like receptor agonists. Temperature of iBAT and tail artery blood flow were measured in conscious rats. Activity in postganglionic sympathetic nerves supplying iBAT was assessed in anesthetized rats. Conscious rats were housed in a warm cage maintained at 26–28 °C and then transferred to a cold cage at 5–10 °C to induce iBAT thermogenesis. Cold exposure increased iBAT temperature (+0.7±0.1 °C, 30 min after transferring to the cold cage, P<0.01, n=54). The mixed dopamine D2/D3 receptor agonist, 7-hydroxy-2-(di-n-propylamino)tetralin (7-OH-DPAT, 0.5 mg/kg s.c.) reversed the cold-induced increase in iBAT temperature (−2.8±0.2 °C at 30 min after 7-OH-DPAT treatment during cold exposure vs. +0.3±0.1 °C at 30 min after vehicle treatment during cold exposure, n=8). These temperature changes were blocked by pre-treatment with the D2 receptor antagonists spiperone (20 μg/kg i.p.) and L-741,626 (2.5 mg/kg i.p.), but not by the selective D3 receptor antagonist SB-277011A (10 mg/kg i.p.). Another mixed dopamine D2/D3 receptor agonist, quinpirole (0.5 mg/kg s.c.) also reversed cold-induced iBAT thermogenesis, and this effect was also prevented by pre-treatment with spiperone, but not with a peripherally acting dopamine receptor antagonist, domperidone (2 mg/kg s.c.). Neither 7-OH-DPAT nor quinpirole reversed cutaneous vasoconstriction elicited by cold exposure. In anesthetized rats, quinpirole (0.5 mg/kg i.v.) abolished iBAT sympathetic nerve discharge elicited by cooling the trunk, and this change was reversed by spiperone (20 μg/kg i.v.). These results demonstrate that activation of CNS dopamine D2 receptors inhibits sympathetically-mediated iBAT thermogenesis in response to cold exposure. Furthermore, they suggest that in rats hypothermia induced by dopamine D2 receptor agonists in cold environments is mainly due to decreased heat production rather than to increased heat loss.