Contrasting effects of bromocriptine on learning of a partially baited radial arm maze task in the presence and absence of restraint stress.
BACKGROUND
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 D(2) receptor agonist, bromocriptine, has been shown to modulate learning, and chronic stress is associated with dopaminergic dysfunction.


OBJECTIVE
In the present study, we evaluated the effects of bromocriptine in the presence or absence of restraint stress.


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.
Srikumar
B N
BN
Department of Neurophysiology, National Institute of Mental Health and Neuro Sciences, Bangalore, India.
Raju
T R
TR
Shankaranarayana Rao
B S
BS
D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D001971:Bromocriptine / Q000494:pharmacology* / Q000627:therapeutic use; D004298:Dopamine / Q000378:metabolism*; D018491:Dopamine Agonists / Q000494:pharmacology* / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D008297:Male; D018782:Maze Learning / Q000187:drug effects*; D008568:Memory / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D012149:Restraint, Physical; D013315:Stress, Psychological / Q000188:drug therapy / Q000209:etiology
D018491:Dopamine Agonists; D001971:Bromocriptine; D004298:Dopamine