Abstract
These experiments investigated the effects of central noradrenaline (NA) depletion and its interaction with cholinergic and dopaminergic mechanisms upon retention of a passive-avoidance response in mice. The NA selective neurotoxin N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine (DSP 4) (50 mg/kg IP, 7 days) was injected into mice to produce depletion of NA in frontal cortex, hypothalamus, cerebellum, midbrain and brain stem without any significant change in dopamine (DA) levels in frontal cortex, striatum, hypothalamus and midbrain. Depletion of brain NA produced by DSP 4 was significantly but not completely prevented by the NA uptake inhibitor desmethylimipramine (DMI) (10 mg/kg IP, 30 min before DSP 4 injection). Despite the marked NA depletion, DSP 4 neither impaired the retention of a passiveavoidance response in mice nor prevented the enhancement of retention of this response induced by the central muscarinic agonist oxotremorine (OTM) (0.05 mg/kg IP, immediately after training. This lack of effect of DSP 4 on retention was prevented neither by DMI nor by the serotonin uptake inhibitor fluoxetine (5 mg/kg IP, 30 min before DSP 4 injection). The enhancement of retention induced by OTM in the groups of mice injected with either water or DSP 4 was prevented by atropine (0.5 mg/kg IP, 20 min before training) but not by methylatropine in the same experimental conditions. This suggests that both in controls and DSP 4-pretreated mice, the primary effect of OTM is due to an interaction with muscarinic brain receptors. Dopaminergic mechanisms were also implicated, since the enhancement of retention induced by OTM was prevented by haloperidol (0.5 mg/kg IP, 120 min before training) and pimozide, in the same experimental conditions, both in control and in DSP 4-pretreated groups. The present data suggest that the effect of OTM upon retention of the passive-avoidance response in mice is mediated via central DA and not NA neurons.
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Introini, I.B., Baratti, C.M. & Huygens, P. Selective brain noradrenaline depletion induced by the neurotoxin N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine (DSP 4) does not prevent the memory facilitation induced by a muscarinic agonist in mice. Psychopharmacology 82, 107–112 (1983). https://doi.org/10.1007/BF00426391
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DOI: https://doi.org/10.1007/BF00426391