A functional effect of dopamine in the nucleus accumbens and in some other dopamine-rich parts of the rat brain

Dopamine (5 to 50 Μg) applied bilaterally to the nucleus accumbens of reserpine-nialamide pretreated rats produced a marked dose-dependent rise in coordinated locomotor activity, devoid of stereotypies such as gnawing, rearing and licking seen after dopamine application (50 Μg) to the neostriatum. The locomotor activity was completely blocked by pimozide, but not by phenoxybenzamine. The effects of apomorphine or d-noradrenaline were similar to those of dopamine. In contrast, l-noradrenaline produced a “convulsive” syndrome devoid of coordinated locomotor activity, and this convulsive syndrome could be completely blocked by phenoxybenzamine but not by pimozide. Release of endogenous dopamine by d- or l-amphetamine (10 and 50 Μg) in the nucleus accumbens produced a rise in coordinated activity, the d-isomer was about 4 times as potent as the l-isomer, and the effect of the d-isomer was blocked completely by α-methyltyrosine. Bilateral application of trifluoperazine (2.5 Μg) to the nucleus accumbens completely blocked the effect of systemically administered d-amphetamine (1.5 and 3.0 mg/kg), but similar application to the area of the central nucleus of the amygdala or the neostriatum was much less effective. Partial protection of the endogenous dopamine stores against the depleting action of reserpine by local application of metatyramine to the nucleus accumbens resulted in a higher level of basal activity than in control animals. Application of dopamine or noradrenaline to the area of the central nucleus of the amygdala or to the olfactory tubercles did not lead to any consistent changes in locomotor activity.The nucleus accumbens and olfactory tubercles contained most of the dopamine in the limbic forebrain, with noradrenaline more evenly distributed.These data suggest that the nucleus accumbens plays an important role in the locomotor activity in rats.

[1]  C. Smith,et al.  ENHANCEMENT BY RESERPINE AND ALPHA-METHYL DOPA OF THE EFFECTS OF D-AMPHETAMINE UPON THE LOCOMOTOR ACTIVITY OF MICE. , 1963, The Journal of pharmacology and experimental therapeutics.

[2]  J. Haeggendal AN IMPROVED METHOD FOR FLUORIMETRIC DETERMINATION OF SMALL AMOUNTS OF ADRENALINE AND NORADRENALINE IN PLASMA AND TISSUES. , 1963, Acta physiologica Scandinavica.

[3]  Y. Kakimoto,et al.  FORMATION OF BETA-PHENYLETHYLAMINE IN MAMMALIAN TISSUE AND ITS EFFECT ON MOTOR ACTIVITY IN THE MOUSE. , 1964, The Journal of pharmacology and experimental therapeutics.

[4]  A. Weissman,et al.  Behavioral effects of L-α-methyltyrosine, an inhibitor of tyrosine hydroxylase , 1965 .

[5]  K. Fuxe,et al.  EVIDENCE FOR THE EXISTENCE OF MONOAMINE NEURONS IN THE CENTRAL NERVOUS SYSTEM. IV. DISTRIBUTION OF MONOAMINE NERVE TERMINALS IN THE CENTRAL NERVOUS SYSTEM. , 1965, Acta physiologica Scandinavica. Supplementum.

[6]  N. Andén,et al.  A quantitative study on the nigro-neostriatal dopamine neuron system in the rat. , 1966, Acta physiologica Scandinavica.

[7]  A. Lundberg,et al.  The effect of DOPA on the spinal cord. 2. A pharmacological analysis. , 1966, Acta physiologica Scandinavica.

[8]  H. Grobecker,et al.  Effect of ß-phenylethylamine on content and subcellular distribution of norepinephrine in rat heart and brain , 1966 .

[9]  A. Randrup,et al.  Role of Catecholamines in the Amphetamine Excitatory Response , 1966, Nature.

[10]  C. Niemegeers,et al.  Pimozide, a chemically novel, highly potent and orally long-acting neuroleptic drug. I. The comparative pharmacology of pimozide, haloperidol, and chlorpromazine. , 1968, Arzneimittel-Forschung.

[11]  P. Janssen,et al.  Pimozide, a chemically novel, highly potent and orally long-acting neuroleptic drug. 3. Regional distribution of pimozide and of haloperidol in the dog brain. , 1968, Arzneimittel-Forschung.

[12]  U. Ungerstedt,et al.  Direct chemical stimulation of dopaminergic mechanisms in the neostriatum of the rat. , 1969, Brain research.

[13]  O. Benkert Measurement of hyperactivity in rats in a dose-response-curve after intrahypothalamic norepinephrine injection. , 1969, Life sciences.

[14]  J. Harvey,et al.  Lesions in the nuclei accumbens septi of the rat: behavioral and neurochemical effects. , 1970, Journal of comparative and physiological psychology.

[15]  K. Fuxe,et al.  Protection of the neostriatal dopamine stores against reserpine by local treatment with metatyramine. , 2009, Acta pharmacologica et toxicologica.

[16]  U. Ungerstedt,et al.  Receptor activity and turnover of dopamine and noradrenaline after neuroleptics. , 1970, European journal of pharmacology.

[17]  T. Magnusson,et al.  Individual elution of noradrenaline (together with adrenaline), dopamine, 5‐hydroxytryptamine and histamine from a single, strong cation exchange column, by means of mineral acid‐organic solvent mixtures , 1970, The Journal of pharmacy and pharmacology.

[18]  D. Segal,et al.  Behavioral activation of rats during intraventricular infusion of norepinephrine. , 1970, Proceedings of the National Academy of Sciences of the United States of America.

[19]  G. Gessa,et al.  Behavioral and vegetative effects produced by dibutyryl cyclic AMP injected into different areas of the brain. , 1970, Advances in biochemical psychopharmacology.

[20]  D. Jackson,et al.  -Phenylethylamine as a cardiotonic constituent of tissue extracts. , 1970, Comparative and general pharmacology.

[21]  H. Hippius,et al.  Kritische Stellungnahme zum Begriff der Neuroleptika , 1971 .

[22]  Z. Kleinrok,et al.  The spontaneous motility of rats after intraventricular injection of dopamine. , 1972, Neuropharmacology.

[23]  P. Greengard,et al.  Dopamine-sensitive adenylate cyclase in caudate nucleus of rat brain, and its similarity to the "dopamine receptor". , 1972, Proceedings of the National Academy of Sciences of the United States of America.

[24]  The effect of β‐phenethylamine upon spontaneous motor activity in mice: A dual effect on locomotor activity , 1972, The Journal of pharmacy and pharmacology.

[25]  R. Naylor,et al.  Modification of the behavioural changes induced by amphetamine in the rat by lesions in the caudate nucleus, the caudate-putamen and globus pallidus. , 1972, Neuropharmacology.

[26]  J. Scheel-Krüger,et al.  Behavioural and biochemical comparison of amphetamine derivatives, cocaine, benztropine and tricyclic anti-depressant drugs. , 1972, European journal of pharmacology.

[27]  J. V. van Rossum,et al.  Ergometrine induced locomotor activity following intracerebral injection into the nucleus accumbens. , 1973, Brain research.

[28]  Z. Herman Behavioural effects of dibutyryl cyclic 3',5' AMP, noradrenaline and cyclic 3',5' AMP in rats. , 1973, Neuropharmacology.

[29]  J. Rossum,et al.  Stimulation of locomotor activity following injection of dopamine into the nucleus accumbens , 1973, The Journal of pharmacy and pharmacology.

[30]  C. Atack The determination of dopamine by a modification of the dihydroxyindole fluorimetric assay , 1973, British journal of pharmacology.

[31]  H. Sabelli,et al.  Phenylethylamine hypothesis of affective behavior. , 2015, The American journal of psychiatry.

[32]  R. Miller,et al.  DOPAMINE IN THE MESOLIMBIC SYSTEM OF THE RAT BRAIN: ENDOGENOUS LEVELS AND THE EFFECTS OF DRUGS ON THE UPTAKE MECHANISM AND STIMULATION OF ADENYLATE CYCLASE ACTIVITY , 1974, Journal of neurochemistry.

[33]  E. Stone,et al.  Effect of intraventricular amines on motor activity in hypothermic rats. , 1974, Research communications in chemical pathology and pharmacology.

[34]  D. Jackson Beta-phenylethylamine and locomotor activity in mice. Interaction with catecholaminergic neurones and receptors. , 1975, Arzneimittel-Forschung.

[35]  Jackson Dm Beta-phenylethylamine and locomotor activity in mice. Interaction with catecholaminergic neurones and receptors. , 1975 .

[36]  Joachim F. R. König,et al.  The rat brain: A stereotaxic atlas of the forebrain and lower parts of the brain stem , 1986 .

[37]  O. Benkert,et al.  Intrahypothalamic and intrastriatal dopamine and norepinephrine injections in relation to motor hyperactivity in rats , 2004, Psychopharmacologia.

[38]  T. Svensson,et al.  An investigation of a new instrument to measure motor activity of small animals , 2004, Psychopharmacologia.

[39]  H. Pakkenberg,et al.  Lesions in corpus striatum and cortex of rat brains and the effect on pharmacologically induced stereotyped, aggressive and cataleptic behaviour , 2004, Psychopharmacologia.

[40]  L. Hanson Evidence that the central action of amphetamine is mediated via catecholamines , 2004, Psychopharmacologia.

[41]  T. Svensson Functional and biochemical effects of d- and l-amphetamine on central catecholamine neurons , 2005, Naunyn-Schmiedebergs Archiv für Pharmakologie.