Effects of central noradrenaline depletion by the selective neurotoxin DSP-4 on the behaviour of the isolated rat in the elevated plus maze and water maze

Abstract.

Rationale: Social isolation of the rat from weaning influences behaviour following central noradrenaline (NA) depletion by the selective neurotoxin N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine (DSP-4). Objectives: The study characterised the effects of DSP-4 on the behaviour of isolates in the elevated plus maze and water maze. Methods: Male Lister hooded rats were reared singly or in groups after weaning. Two weeks postweaning, the rats were injected with DSP-4 (25 mg/kg, i.p.) or saline. From week 4, rats were tested in the plus maze and in the water maze. Results: DSP-4 significantly reduced cortical and hippocampal NA but had no effect on hypothalamic NA. Isolation rearing alone had no significant effects on behaviour in the elevated plus maze but enhanced retention of platform placement in the water maze as measured by increased entries to the platform annulus during the probe test. DSP-4 in group-reared rats increased activity in the open arms and increased general activity in the elevated plus maze with no effect on water maze performance. DSP-4-treated isolates spent less time in the open arms and were hypoactive in the plus maze compared to group-reared DSP-4-treated rats, and had impaired retention of spatial memory in the water maze compared to isolate controls. Conclusions: DSP-4 treatment had an 'anxiolytic' effect in group-reared rats in the elevated plus maze. In the water maze, isolation rearing enhanced retention of spatial information, an effect normalised by NA depletion. The results demonstrate the importance of noradrenergic function in the regulation of responsiveness to environmental cues.