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

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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.

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Acknowledgement

Bromocriptine was a generous gift from the Serum Institute of India, Mumbai, India. The authors thank Titus, Bindu and Harsha for their technical assistance in the neurochemistry experiments; Bhagya and Veena for their help in data entry.

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  1. B. N. Srikumar

    Present address: Department of Physiology, University of Utah School of Medicine, Salt Lake City, UT, 84108, USA

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  1. Department of Neurophysiology, National Institute of Mental Health and Neuro Sciences (NIMHANS), PB# 2900, Hosur Road, Bangalore, 560 029, India

    B. N. Srikumar, T. R. Raju & B. S. Shankaranarayana Rao

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Srikumar, B.N., Raju, T.R. & Shankaranarayana Rao, B.S. Contrasting effects of bromocriptine on learning of a partially baited radial arm maze task in the presence and absence of restraint stress. Psychopharmacology 193, 363–374 (2007). https://doi.org/10.1007/s00213-007-0801-4

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