Environment-specific reinstatement of amphetamine-mediated hyperdipsia by morphine and (-)-norpseudoephedrine

In a study designed to determine whether environmental and pharmacological stimuli have the ability to take control of amphetamine-mediated hyperdipsia, rats were injected with d,l-amphetamine (AMPH; 4 mg/kg, IP) alone or in combination with (-)-norpseudoephedrine (NPE; 10 mg/kg, IP) and then returned to the home cage or transferred to a distinct environment (test cage). Water intake was measured hourly for 3 h, in the absence of food. AMPH treatment lasted for 10 days, followed by a 6-day extinction phase during which AMPH, but not NPE, injections were discontinued. Subsequently, all animals received challenge injections: NPE (10 mg/kg) on day 17; AMPH (4 mg/kg) on day 19; and morphine (MOR; 1 mg/kg) on day 21. AMPH-mediated hyperdipsia developed in 50% of animals and had an early onset in the home cage. NPE prevented the AMPH effects. Discontinuation of AMPH treatment promptly normalized drinking in the home cage but increased it further in the test cage. Within 6 days of AMPH discontinuation, hyperdipsia completely disappeared. It was reinstated, in the test cage alone, by a challenge injection of NPE or MOR. We suggest that hyperdipsia is a primary AMPH effect, which in some way is counter-acted by a distinct environment. This appears to elicit a compensatory mechanism that is revealed in the absence of AMPH and is reinstated in a nonspecific way by pharmacological stimuli.