Dissociation in the modulatory effects of environmental novelty on the locomotor, analgesic, and eating response to acute and repeated morphine in the rat.

RATIONALE: We have previously shown that environmental novelty can potentiate the activating effects of morphine and the development of sensitization to this effect. OBJECTIVES. Our main goal was to determine whether environmental novelty can also modulate the prophagic (time spent eating and food intake; experiment 1) and/or the analgesic (tail-flick test; experiments 2 and 3) effect of morphine, as well as the development of tolerance or sensitization to these effects. METHODS: In experiment 1, two groups of rats were administered seven intraperitoneal (i.p.) injections of either saline or morphine (4.0 mg/kg) either in their home cages (home groups) or in a distinct environment (novelty groups). After 7 days of withdrawal, both groups underwent a morphine challenge (4.0 mg/kg, i.p.). In experiment 2, home and novelty rats were administered four doses of morphine (0.0, 2.0, 4.0, and 8.0 mg/kg, i.p.) following a counterbalanced order. In experiment 3, home and novelty rats were administered eight intraperitoneal (i.p.) injections of either saline or morphine (8.0 mg/kg) and then given a morphine challenge (4.0 mg/kg). RESULTS: Environmental novelty enhanced the locomotor activating effect of morphine and the expression of sensitization to this effect (even after a period of withdrawal). Environmental novelty had relatively little effect on morphine-induced eating, and no effect on morphine-induced analgesia. CONCLUSIONS: Environmental context can have very different consequences on distinct drug effects as well as on distinct neurobehavioral adaptations to the same drug treatment (e.g., psychomotor sensitization versus analgesic tolerance).

Dissociation in the effects of the D2/D3 dopaminergic agonist quinpirole on drinking and on vasopressin levels in the rat.

In the present study, we investigated the role of vasopressin in the development of quinpirole-induced hyperdipsia in the rat. We report that: (1), an acute intraperitoneal (i.p.) injection of 0.56 mg/kg of quinpirole increased plasma vasopressin (radioimmunoassay) at 15 min but not at 30 or 120 min; (2), nine daily injections of quinpirole (0.56 mg/kg, i.p.) progressively increased water intake and diuresis for a period of several hours after each treatment; (3), quinpirole hyperdipsia was associated with apparently normal levels of vasopressin (which might be considered inappropriately high in the presence of excessive drinking); (4), quinpirole reduced vasopressin and oxytocin, but not angiotensin, immunoreactivity in the supraoptic nucleus. These findings suggest that quinpirole hyperdipsia is a sound animal model of psychotic polydipsia.