Central serotonin neurones in avoidance learning: interactions with noradrenaline and dopamine neurones

The effects of p-chloroamphetamine (PCA), a serotonin (5-HT) releaser, on acquisition and retention were examined in male Sprague-Dawley rats using a one-way active avoidance task. PCA was found to impair avoidance acquisition and retention in a time dependent fashion which followed closely the temporal effects of the drug on 5-HT release in the brain. Thus, the avoidance deficit is related to the rate of change and not to the steady-state levels of 5-HT. The 5-HT releasing effect was most pronounced in the forebrain with less effect in the spinal cord. PCA caused time dependent, regional variations in catecholamine content, which was not related to avoidance performance. The avoidance and retention impairment induced by PCA was blocked by the 5-HT synthesis inhibitor p-chlorophenylalanine (PCPA) but not by depletion of catecholamines with alpha-methyl-p-tyrosine (H44/68) or by the noradrenergic-selective neurotoxin DSP4. Analysis of the time dependent effects of PCA on monoamine content in saline or PCPA-treated rats indicated that the temporal effects of PCA on avoidance performance is not due to a direct or indirect action on catecholamine neurones. The present experiments support the view that the ascending serotonergic pathways play a significant role in aversive learning in the rat.