Neuroleptic inhibition of 6,7-ADTN-induced hyperactivity after injection into the nucleus accumbens. Specificity and comparison with other models. 1983

J Arnt

The dopamine agonist 6,7-ADTN induced locomotor stimulation after injection into the nucleus accumbens of rats. This hyperactivity was stereospecifically antagonized by peripheral injection of typical and atypical neuroleptics, except sulpiride, regardless of structural class. The potency of 14 neuroleptics correlated significantly to that in other neuroleptic in vivo models in rats, i.e. cataleptogenic and amphetamine-antagonistic (stereotypy, circling) activity. Sulpiride was inactive after peripheral injection, whereas intraacumbens sulpiride antagonized 6,7-ADTN-induced hyperactivity with a higher potency than that found for locally injected cis-(Z)-flupentixol, haloperidol and clebopride. Blockade of alpha 1-adrenergic receptors by systemic prazosin or locally injected phentolamine also antagonized 6,7-ADTN, whereas antagonists of alpha 2-adrenergic, beta-adrenergic, muscarinic and serotoninergic receptors were without effect. Furthermore, the cis-(Z)-flupentixol and haloperidol-induced 6,7-ADTN blockade was only slightly or not reversed by additional antimuscarinic (scopolamine) or antiserotonergic (methysergide) treatment. It is concluded that antagonism of 6,7-ADTN-induced hyperactivity is a relevant model for detecting neuroleptic activity with minimal influence of anticholinergic and antiserotonergic activity, but that the dopamine receptor within the nucleus accumbens responsible for the locomotor stimulation is similar to that involved in other behavioural effects of neuroleptics. It is suggested that an apparent preferential limbic action of some neuroleptics (e.g. clozapine and chlorprothixene) is more likely to be explainable by their simultaneous blocking effect on dopaminergic, alpha-adrenergic and muscarinic receptors.

UI MeSH Term Description Entries
D007267 Injections Introduction of substances into the body using a needle and syringe. Injectables,Injectable,Injection
D008297 Male Males
D009043 Motor Activity Body movements of a human or an animal as a behavioral phenomenon. Activities, Motor,Activity, Motor,Motor Activities
D009281 Naphthalenes Two-ring crystalline hydrocarbons isolated from coal tar. They are used as intermediates in chemical synthesis, as insect repellents, fungicides, lubricants, preservatives, and, formerly, as topical antiseptics.
D009714 Nucleus Accumbens Collection of pleomorphic cells in the caudal part of the anterior horn of the LATERAL VENTRICLE, in the region of the OLFACTORY TUBERCLE, lying between the head of the CAUDATE NUCLEUS and the ANTERIOR PERFORATED SUBSTANCE. It is part of the so-called VENTRAL STRIATUM, a composite structure considered part of the BASAL GANGLIA. Accumbens Nucleus,Nucleus Accumbens Septi,Accumbens Septi, Nucleus,Accumbens Septus, Nucleus,Accumbens, Nucleus,Nucleus Accumbens Septus,Nucleus, Accumbens,Septi, Nucleus Accumbens,Septus, Nucleus Accumbens
D011919 Rats, Inbred Strains Genetically identical individuals developed from brother and sister matings which have been carried out for twenty or more generations or by parent x offspring matings carried out with certain restrictions. This also includes animals with a long history of closed colony breeding. August Rats,Inbred Rat Strains,Inbred Strain of Rat,Inbred Strain of Rats,Inbred Strains of Rats,Rat, Inbred Strain,August Rat,Inbred Rat Strain,Inbred Strain Rat,Inbred Strain Rats,Inbred Strains Rat,Inbred Strains Rats,Rat Inbred Strain,Rat Inbred Strains,Rat Strain, Inbred,Rat Strains, Inbred,Rat, August,Rat, Inbred Strains,Rats Inbred Strain,Rats Inbred Strains,Rats, August,Rats, Inbred Strain,Strain Rat, Inbred,Strain Rats, Inbred,Strain, Inbred Rat,Strains, Inbred Rat
D011954 Receptors, Dopamine Cell-surface proteins that bind dopamine with high affinity and trigger intracellular changes influencing the behavior of cells. Dopamine Receptors,Dopamine Receptor,Receptor, Dopamine
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D006892 Hydroxydopamines Dopamines with a hydroxy group substituted in one or more positions. Hydroxydopamine
D000661 Amphetamine A powerful central nervous system stimulant and sympathomimetic. Amphetamine has multiple mechanisms of action including blocking uptake of adrenergics and dopamine, stimulation of release of monamines, and inhibiting monoamine oxidase. Amphetamine is also a drug of abuse and a psychotomimetic. The l- and the d,l-forms are included here. The l-form has less central nervous system activity but stronger cardiovascular effects. The d-form is DEXTROAMPHETAMINE. Desoxynorephedrin,Levoamphetamine,Phenopromin,l-Amphetamine,Amfetamine,Amphetamine Sulfate,Amphetamine Sulfate (2:1),Centramina,Fenamine,Mydrial,Phenamine,Thyramine,levo-Amphetamine,Sulfate, Amphetamine,l Amphetamine,levo Amphetamine

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