Abstract
Mice permitted to explore an 8-arm radial maze tended to visit those arms least recently entered. Treatment with d-amphetamine engendered a perseverative tendency, wherein mice repeatedly visited two arms of the maze. Administration of the norepinephrine (NE) neurotoxin, N-2-chloroethyl-N-ethyl-2-bromo-benzylamine (DSP4), appreciably reduced NE in the hippocampus and cortex, moderately reduced NE in the locus coeruleus, and had only a small effect on hypothalamic NE. The DSP4 treatment resulted in a decrease of locomotor activity among amphetaminetreated mice, coupled with an increase of stereotyped response patterns. Although the NE depletion did not affect the pattern of exploration that mice ordinarily displayed, DSP4 appreciably increased the perseverative tendency provoked by amphetamine. Reduction of dopamine (DA) and NE by intraventricular administration of the catecholamine neurotoxin, 6-hydroxydopamine (6-OHDA), antagonized the effects of amphetamine, such that the frequency of alternation responses was increased and the proportion of perseverative responses was reduced. The effectiveness of the 6-OHDA treatment in antagonizing the amphetamine-induced perseveration was not reduced among mice that were pretreated with desmethylimipramine, which resulted in partial prevention of the NE reduction by 6-OHDA administration. It is suggested that DA neuronal activity contributes to the amphetamineprovoked perseveration, whereas NE stimulation modifies the perseverative tendency by influencing exploration or habituation.
Similar content being viewed by others
References
Anisman H, Santi A (1981) Behavioral techniqes in pharmacological and neuropharmacological analysis. In: Lahue R (ed) Methods in neurobiology. Plenum Press, New York
Anisman H, Sklar LS (1981) Social housing conditions influence escape deficits produced by uncontrollable stress: Assessment of the contribution of norepinephrine. Behav Neurol Biol 32:406–427
Antelman SH, Caggiula AR (1977) Norepinephrine-dopamine interactions and behavior. Science 195:646–653
Brainbridge JG (1970) The inhibitory effect of amphetamine on exploration in mice. Psychopharmacologia 18:314–319
Bruto V, Kokkinidis L, Anisman H (1983) Attenuation of perseverative behavior after repeated amphetamine treatment: Tolerance or attentional deficits? Pharmacol Biochem Behav 19:497–504
Carlton PL (1969) Brain acetylcholine and inhibition. In: Tapp JT (ed) Reinforcement and behavior. Academic Press, New York
Douglas RJ (1975) The development of hippocampal functions: Implications for theory and therapy. In: Isaacson RL, Pribram KH (eds) The hippocampus, vol 2, Neurophysiology and behavior. Plenum Press, New York
Douglas RJ, Isaacson RL (1966) spontaneous alternation and scopolamine. Psychon Sci 4:283–284
Drew WG, Miller LL, Baugh EL (1973) Effects of Δ9-THC, LSD-25 and scopolamine on continuous spontaneouss alternation in the Y-maze. Psychopharmacologia 32:171–182
Eckerman DA, Gordon WA, Edwards JD, MacPhail RC, Gage MI (1980) Effects of scopolamine, pentobarbital and amphetamine on radial maze performance in the rat. Pharmacol Biochem Behav 12:595–602
Einon D (1980) Spatial memory and response strategies in rats: Age, sex and rearing differences in performance. Q J Exp Psychol 32:473–489
Einon DF, Sahakian BJ (1979) Environmentally induced differences in susceptibility of rats to CNS stimulants and CNS depressants: Evidence against a unitary explanation. Psychopharmacology 61:299–307
File SE, Pope JH (1974) Social interaction between drugged and undrugged rats. Anim Learn Behav 2:161–164
File SE, Wardill AG (1975) Validity of head-dipping as a measure of exploration in a modified hole board. Psychopharmacologia 44:53–59
Fink JS, Smith GP (1979a) Decreased locomotor and investigatory exploration after denervation of catecholamine terminal fields in the forebrain of rats. J Comp Physiol Psychol 93:34–65
Fink JS, Smith GP (1979b) l-Dopa repairs deficits in locomotor and investigatory exploration produced by denervation of catecholamine terminal fields in the forebrain of rats. J Comp Physiol Psychol 93:66–73
Jaim-Etcheverry G, Zieher LM (1980) DSP-4: A novel compound with neurotoxic effects on noradrenaline neurons of adult and developing rats. Brain Res 188:513–523
Jerussi TP, Glick SD (1974) Amphetamine-induced rotation in rats without lesions. Neuropharmacology 13:283–286
Jerussi TP, Glick SD (1976) Drug-induced rotation in rats without lesions: Behavioral and neurochemical indices of a normal asymmetry in nigro-striatal function. Psychopharmacology 47:249–260
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
Kokkinidis L, Anisman H (1976a) Dissociation of the effects of scopolamine and d-amphetamine on a spontaneous alternation task. Pharm Biochem Behav 5:293–297
Kokkinidis L, Anisman H (1976b) Interaction between cholinergic and catecholaminergic agents in a spontaneous alternation task. Psychopharmacology 48:261–270
Kokkinidis L, Anisman H (1977) Perseveration and rotational behavior elicited by d-amphetamine in a Y-maze exploratory task: Differential effects of intraperitoneal and unilateral intraventricular administration. Psychopharmacology 52: 123–128
Kokkinidis L, Anisman H (1978) Behavior-specific tolerance following chronic d-or l-amphetamine treatment: Lack of involvement of p-hydroxynorephedrine. Neuropharmacology 17: 95–102
Kokkinidis L, Anisman H (1979) Circling behavior after acute and chronic systemic d-amphetamine treatment: Potential noradrenergic and dopaminergic involvement. Psychopharmacology 64:45–54
Kokkinidis L, Anisman H (1980) Amphetamine models of paranoid schizophrenia: An overview and elaboration of animal experimentation. Psychol Bull 88:551–579
Kokkinidis L, MacNeill EP (1982) Stress-induced facilitation of acoustic startle after d-amphetamine administration. Pharm Biochem Behav 17:413–417
Kokkinidis L, Irwin J, Anisman H (1979) Shock-induced locomotor excitation following acute and chronic amphetamine treatment. Neuropharmacology 18:13–22
Laverty R, Taylor KM (1968) Fluorometric assay for catecholamines and related compounds: Improvements and extension of the hydroxyindole technique. Anal Biochem 22:269–279
Maickel RF, Cox RH, Saillant J, Miller FP (1968) A method for the determination of serotonin and norepinephrine in discrete areas of rat brain. Int J Neuropharmacol 7:275
Misslin R, Ropartz P (1981) Effects of methamphetamine on novelty seeking behavior. Psychopharmacology 75:39–43
Modigh K (1976) Influence of social stress on catecholamine mechanisms. In: Usdin E, Kvetnansky R, Kopin IJ (eds) Catecholamines and stress. Pergamon Press, Oxford
Mogilnicka E, Braestrup C (1976) Noradrenergic influence on the stereotyped behavior induced by amphetamine, phenethylamine and apomorphine. J Pharm Pharmacol 28:253–255
Olton DS, Samuelson RJ (1976) Remembrance of places past: Spatial memory in rats. J Exp Psychol [Anim Behav] 2:97–116
Ogren SO, Archer T, Ross SB (1980) Evidence for a role of the locus coeruleus noradrenaline system in learning. Neurosci Lett 20:351–356
Robbins T, Iversen SD (1973) Dissociation of the effects of d-amphetamine on locomotor activity and exploration in rats. Psychopharmacologia 28:155–164
Sahakian BJ, Robbins TW, Morgan MJ, Iversen SD (1975) The effects of psychomotor stimulants on stereotypy and locomotor activity in socially deprived and control rats. Brain Res 84:195–200
Stevens R, Cowey A (1973) Effects of dorsal and ventral hippocampal lesions on spontaneous alternation, learned alternation and probability learning in rats. Brain Res 52:203–224
Swonger AK, Rech RH (1972) Serotonergic and cholinergic involvement in habituation of activity and spontaneous alternation of rats in a Y-maze. J Comp Physiol Psychol 81:509–522
Welch BL, Welch AS (1970) Control of brain catecholamines and serotonin during acute stress and after d-amphetamine by natural inhibition of monoamine oxidase: An hypothesis. In: Costa E, Garattini S (eds) Amphetamines and related compounds. Raven Press, New York
Wendlandt S, File SI (1979) Behavioral effects of lesions of the locus coeruleus noradrenaline system combined with adrenalectomy. Behav Neurol Biol 26:189–201
White SR (1974) Atropine, scopolamine and hippocampal lesion effects on alternation performance of rats. Pharm Biochem Behav 2:297–308
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Bruto, V., Beauchamp, C., Zacharko, R.M. et al. Amphetamine-induced perseverative behavior in a radial arm maze following DSP4 or 6-OHDA pretreatemnt. Psychopharmacology 83, 62–69 (1984). https://doi.org/10.1007/BF00427424
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF00427424