Abstract
Rats were given four inescapable shocks (1.0 mA) when confined to the right-hand corner of a modified shuttlebox. p-Chloroamphetamine (PCA) injected just before the retention test 24 h later completely blocked the immobile posture that was observed after saline injections. This retention deficit was shown to be selectively associated with 5-hydroxytryptamine (5-HT) release, since the administration of the 5-HT uptake inhibitors zimelidine and citalopram 60 min prior to PCA antagonized this effect. The 5-HT specificity of the deficit was further established by the findings that 5-HT-depleted rats (PCA, 2×10 mg/kg, and fenfluramine, 2×25 mg/kg), but not NA-depleted rats (DSP4, 1×50 mg/kg), or rats treated with zimelidine (2×20 mg/kg) 60 min before PCA (2×10 mg/kg), showed an almost complete blockade of the retention failure. The data presented may provide a useful experimental model for investigating the efficacy of functional 5-HT activity in the treatment of phobic anxiety.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Archer T (1982) Serotonin and fear retention in the rat. J Comp Physiol Psychol 96:491–516
Archer T, Ögren SO, Johanson C (1981) The acute effect of p-chloro-amphetamine on the retention of fear conditioning in the rat: Evidence for a role of serotonin in memory consolidation. Neurosci Lett 25:75–81
Carey MS, Hawkinson R, Karnhaber A, Wellish CS (1975) The use clomipramine in phobic patients. Curr Ther Res 17:107–110
Essman WB (1973) Neuromolecular modulation of experimentally induced retrograde amnesia. Confinia Neurologica 35:1–2
Fuller RW, Perry KW, Molloy BB (1974) Effect of an uptake inhibitor on serotonin metabolism in rat brain: studies with 3-(p-trifluoromethylphenoxy)-N-methyl-3-phenyl-propylamine (Lilly 1101040). Life Sci 15:1161–1171
Fuller RW, Perry KW, Molloy BB (1975) Reversible and irreversible phases of serotonin depletion by 4-chloroamphetamine. Eur J Pharmacol 33:119–124
Harvey JA (1978) Neurotoxic action of halogenated amphetamines. Ann N Y Acad Sci 305:289–304
Harvey JA, McMaster SE (1976) Neurotoxic action of parachloroamphetamine in the rat as revealed by Nissl and silver stains. Psychopharmacol Bull 12:62–64
Harvey JA, McMaster SE (1975) Fenfluramine: Evidence for a neurotoxic action on midbrain and a long-term depletion of serotonin. Psychopharm Commun 1:217–228
Harvey JA, McMaster SE, Yunger LM (1975) p-chloroamphetamine: Selective neurotoxic action in brain. Science 187:841–843
Jaim-Etcheverry G, Zieher LM (1980) DSP4: A novel compound with neurotoxic effects on noradrenergic neurons of adult and developing rats. Brain Res 188:513–523
Jonsson G, Hallman H, Ponzio F, Ross S (1981) DSP4-(N-2-chloroethyl-N-ethyl-2-bromobenzylamine) A useful denervation tool for central and peripheral noradrenaline neurons. Eur J Pharmacol 72:173–188
Joyce D, Hurwitz HMB (1964) Avoidance behaviour in the rat after 5-hydroxytryptophan (5-HTP) administration. Psychopharmacologia 5:424–430
Kilts CD, Commissaris RL, Rech RH (1981) Comparison of anticonflict drug effects in three experimental animal models of anxiety. Psychopharmacology 74:290–296
Koczkas S, Holmberg G, Wedin L (1981) A pilot study of the effect of the 5-HT uptake inhibitor, zimelidine, on phobic anxiety. Acta Psychiatr Scand 63:328–341
Koe BK, Weissman A (1966) p-Chlorophenylalanine: A specific depletor of brain serotonin. J Pharmacol Exp Ther 154:499–516
Magnusson O, Nilsson LB, Westerlund D (1980) Simultaneous determination of dopamine, dopac and homovanillic acid. Direct injection of supernatants from brain tissue homogenates in a liquid chromatography-electrochemical detection system. J Chromatogr 221:237–247
Ögren SO (1982a) Central serotonin neurons and learning in the rat. In: Osborne NN (ed) Biology of serotonergic transmission. John Wiley & Sons, London, pp 317–334
Ögren SO (1982b) Forebrain serotonin and avoidance learning: Behavioural and biochemical studies on the acute effect of p-chloroamphetamine on one-way active avoidance learning in the rat. Pharmacol Biochem Behav 16:881–895
Ögren SO, Ross SB, Holm AC, Bauman L (1977) 5-Hydroxytryptamine and avoidance performance in the rat. Antagonism of acute effect of p-chloroamphetamine by zimelidine, an inhibitor of 5-hydroxytryptamine uptake. Neurosci Lett 7:331–336
Pletscher A, Bartholini G, Bruderer H, Buckard WP, Gey KF (1964) Chlorinated aralkylamines affecting the central metabolism of 5-hydroxytryptamine. J Pharmacol Exp Ther 145:344–350
Roffman M, Lal H (1971) Facilitatory effect of amphetamine on learning and recall of an avoidance response on rats. Arch Int Pharmacodyn 193:87–91
Ross SB (1976a) Antagonism of the acute and long-term biochemical effects of 4-chloroamphetamine on the 5-HT neurons in the rat brain by inhibitors of the 5-hydroxytryptamine uptake. Acta Pharmacol Toxicol 39:456–476
Ross SB (1976b) Long-term effects of N-2-chloroethyl-N-ethyl-2-bromobenzylamine hydrochloride on noradrenergic neurons in the rat brain and heart. Br J Pharmacol 58:521–527
Siegel S (1956) Nonparametric statistics for the behavioural sciences. McGraw-Hill, New York
Trulson ME, Jacobs BL (1976) Behavioural evidence of for the rapid release of CNS serotonin by PCA and fenfluramine. Eur J Pharmacol 36:149–154
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Archer, T., Ögren, S.O., Ross, S.B. et al. Retention deficits induced by acute p-chloroamphetamine following fear conditioning in the rat. Psychopharmacology 82, 14–19 (1983). https://doi.org/10.1007/BF00426373
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF00426373