Carbon monoxide exposure reduces the rewarding quality of brain-stimulation reward in rats

The effect of carbon monoxide (CO) exposure on hypothalamic brain-stimulation reward (BSR) was examined. Rats were trained in a procedure that daily determined their stimulus duration threshold (SDT), that is, the shortest electrical stimulus to the posterior lateral hypothalamus that would support discrete-trial leverpress responding for BSR. After a stable SDT baseline was established using a single response lever, rats were exposed to 0, 5, 10, 20, and 40 ml/kg pure CO by IP injection. The SDT was significantly elevated by the 40 ml/kg exposure (corresponding to approximately 65% carboxyhemoglobin in the blood) compared to control exposures of an equal volume. No change was observed in response rate at any dose in this 1-lever task. No tolerance was observed when 40 ml/kg CO exposure was repeated on alternating days for 14 exposures, but a small reduction in response rate was observed in this procedure. When rats of a second group were required to alternate responses on two levers some distance apart, SDT was elevated by the highest exposure (40 ml/kg) as before. Additionally, response rate was also significantly suppressed by the highest exposure in this 2-lever task. The results support the view that CO has a direct effect on brain reward systems assessed by the SDT task. Response rate changes due to CO exposure may be due to both direct effects on brain reward systems and other effects such as hypoxia-induced fatigue.