Contrasting effects of bromocriptine on learning of a partially baited radial arm maze task in the presence and absence of restraint stress

Abstract

Rationale: Severe, traumatic stress or repeated exposure to stress can result in long-term deleterious effects, including hippocampal cell atrophy and death, which, in turn, result in memory impairments and behavioural abnormalities. The dopaminergic D₂ receptor agonist, bromocriptine, has been shown to modulate learning, and chronic stress is associated with dopaminergic dysfunction. Objectives: In the present study, we evaluated the effects of bromocriptine in the presence or absence of restraint stress. Materials and methods: Adult male Wistar rats were subjected to restraint stress for 21 days (6 h/day) followed by bromocriptine treatment, and learning was assessed in the partially baited radial arm maze task. In a separate group of animals, the effects of bromocriptine per se was evaluated. Dopamine levels were estimated by high-performance liquid chromatography with electrochemical detection. Results: Stressed rats showed impairment in both acquisition and retention of the radial arm maze task, and bromocriptine treatment after stress showed a reversal of stress-induced impairment. Interestingly, in the absence of stress, bromocriptine exhibited dose-dependent differential effects on learning. While rats treated with bromocriptine 5 mg/kg, i.p., demonstrated impairment in learning, the bromocriptine 10 mg/kg and vehicle-treated groups did not differ from normal controls. To understand the neurochemical basis for the effects of bromocriptine, dopamine levels were estimated. The stress-induced decrease in dopamine levels in the hippocampus and frontal cortex were restored by bromocriptine treatment. In contrast, bromocriptine alone (5 mg/kg, i.p.) decreased dopamine levels in the frontal cortex and striatum. Conclusions: Our study shows that amelioration of stress-induced learning impairment correlates with restoration of dopamine levels by bromocriptine treatment.