Serotonin neurons and aversive conditioning in the rat

The acute and long-term effects of p -chloroamphetamine (PCA) on one-way and two-way active avoidance (AA), passive avoidance (PA) learning, fear retention (FR) and on central monoamine concentrations were examined in the male rat. Acute PCA administration (0.63–5 mg/kg i.p.), which releases presynaptic 5-HT, produced a dose-related impairment of both one-and two-way AA acquisition, AA retention, PA and fear retention. The selective serotonin (5-HT) uptake inhibitor zimelidine, but not the noradrenaline (NA) uptake inhibitor desipramine, blocked the avoidance deficit induced by acute PCA. Degeneration of brain 5-HT neurons by a high neurotoxic dose of PCA (2 × 10 mg/kg i.p.) failed to change AA and PA learning but blocked the avoidance deficit induced by acute PCA. Degeneration of locus coeruleus NA neurones with DSP4 (1 × 50 mg/kg), a selective NA neurotoxin, failed to block the acute PCA action. Thus, the acute avoidance learning impairment appears to be specifically related to the acute release of endogenous 5-HT. Both acute and long-term PCA treatment affected 5-HT neurones preferentially in the forebrain while marginal effects were observed in the midbrain and spinal cord. A marked impairment in the retention and retrieval of fear conditioning in the rat was also observed following acute PCA administration. The serotoninergic mechanisms underlying the retrieval deficit were found to be similar but not identical to those involved in AA acquisition. These results suggest an important role for central 5-HT neurones in aversive learning processes. The possible involvement of 5-HT neurones in learning, memorial and/or retrieval processes is discussed.