The effect of repeated desipramine administration on water intake in rats

Rats were maintained on a regimen of restricted access to water. Desipramine (DMI) IP 1 h prior to the access period dose-dependently reduced water intake. Following completion of the dose-response determination for the effect of desipramine or water intake, rats were divided into three groups for repeated administration. Rats in each group were injected both 1 h before and 15 min after the access period. The SAL-SAL group received saline both before and after the session, the DMI-SAL group received 10 mg/kg DMI before and saline after the session, and the SAL-DMI group received saline before and 10 mg/kg DMI after the session. Average water intake for rats in the DMI-SAL group decreased progressively during the first 5 days of repeated administration and then began to return toward baseline levels. Average water intake for rats in the SAL-DMI group decreased progressively from days 4-18 of repeated administration and then began to increase toward baseline levels. Rats repeatedly administered DMI (DMI-SAL and SAL-DMI groups) became tolerant to its effect on water intake, as indicated by a diminution of the DMI effect during repeated treatment and by a shift to the right in the DMI dose-response function after discontinuation of repeated DMI administration. Both groups of rats administered DMI repeatedly were less sensitive to amitriptyline-induced reduction of water intake than controls, thereby indicating the development of cross-tolerance to amitriptyline. Cross-tolerance to scopolamine did not develop. These findings demonstrate a behavioral effect of DMI that results in the development of tolerance. The lack of cross-tolerance to scopolamine suggests that tolerance development is not due to altered central cholinergic function.