Effects of noradrenaline depletion in the brain on response to novelty in isolation-reared rats

Rationale: Social isolation from weaning in the rat produces a variety of neurochemical and behavioural effects in the adult that in part parallel changes seen in human schizophrenia. Objectives: The study investigated the effects of central noradrenaline (NA) depletion by the selective neurotoxin, N-(2-chloroethyl)-N ethyl-2-bromobenzylamine (DSP-4), on the behaviour of isolation-reared rats. Methods. Male Lister hooded rats were reared singly or in groups after weaning. During week, the rats were tested in photocell activity cages and were then injected with DSP-4 (25 mg/kg, IP). During week 4, rats were tested in the open field under the following conditions: open field alone, with two novel stimuli (T1), and with a familiar and a novel object (T2), and in the activity cages. Results: DSP-4 significantly reduced cortical and hippocampal NA levels with no effect on the hypothalamus. Isolation-reared rats exhibited locomotor hyperactivity and reduced habituation to the testing arena, although their exploration of the novel objects in T1 was not significantly different from group-reared rats. DSP-4 treatment in group-reared rats increased inner zone activity in the open field but did not significantly affect the exploration of novel objects. DSP-4 treatment in isolates reduced exploration of objects at T2 while increasing exploration of the general environment. Conclusions: Isolation rearing influences the behavioural effects of central NA depletion. The results suggest isolation-induced changes in the central noradrenergic system in the isolated rat, supporting the view that early environmental factors can have long-term effects on central noradrenergic function as well as other neurotransmitter systems.