The behavioural effects of MK-801 in rats: involvement of dopaminergic, serotonergic and noradrenergic systems. 1992

W Löscher, and D Hönack
Department of Pharmacology, Toxicology and Pharmacy, School of Veterinary Medicine, Hannover, F.R.G.

The non-competitive NMDA receptor antagonist, MK-801 (dizocilpine), induces in rats a characteristic behavioural syndrome with ataxia, stereotypies and hyperlocomotion. At least part of this behavioural syndrome is thought to be related to interactions between glutamatergic and dopaminergic neurotransmission. Based on recent biochemical evidence that serotonin (5-HT) might also be involved in the effects of MK-801 several 5-HT receptor ligands were tested for effects on MK-801-induced behaviours. The 5-HT1A receptor ligands, ipsapirone and NAN-190, which are known to display antagonist-like properties in functional models of postsynaptic 5-HT1A receptor activity attenuated or blocked the hyperlocomotion and head weaving observed after administration of MK-801, whereas the 5-HT2 receptor antagonist, ritanserin, was ineffective in this respect. The dopamine receptor antagonist, haloperidol, and the alpha 1-adrenoceptor antagonist, prazosin, also attenuated behaviours induced by MK-801. In contrast to its effects on stereotypies induced by MK-801, ipsapirone potentiated rather than attenuated the stereotyped behaviour induced by the dopamine receptor agonist, apomorphine, indicating that antagonism of MK-801-induced stereotypies by ipsapirone may not be related to the dopaminergic system. The data indicate that, in addition to catecholaminergic systems, serotonergic neurotransmission is significantly involved in the mechanisms by which MK-801 alters behaviour in rats.

UI MeSH Term Description Entries
D008297 Male Males
D009043 Motor Activity Body movements of a human or an animal as a behavioral phenomenon. Activities, Motor,Activity, Motor,Motor Activities
D009638 Norepinephrine Precursor of epinephrine that is secreted by the ADRENAL MEDULLA and is a widespread central and autonomic neurotransmitter. Norepinephrine is the principal transmitter of most postganglionic sympathetic fibers, and of the diffuse projection system in the brain that arises from the LOCUS CERULEUS. It is also found in plants and is used pharmacologically as a sympathomimetic. Levarterenol,Levonorepinephrine,Noradrenaline,Arterenol,Levonor,Levophed,Levophed Bitartrate,Noradrenaline Bitartrate,Noradrénaline tartrate renaudin,Norepinephrin d-Tartrate (1:1),Norepinephrine Bitartrate,Norepinephrine Hydrochloride,Norepinephrine Hydrochloride, (+)-Isomer,Norepinephrine Hydrochloride, (+,-)-Isomer,Norepinephrine d-Tartrate (1:1),Norepinephrine l-Tartrate (1:1),Norepinephrine l-Tartrate (1:1), (+,-)-Isomer,Norepinephrine l-Tartrate (1:1), Monohydrate,Norepinephrine l-Tartrate (1:1), Monohydrate, (+)-Isomer,Norepinephrine l-Tartrate (1:2),Norepinephrine l-Tartrate, (+)-Isomer,Norepinephrine, (+)-Isomer,Norepinephrine, (+,-)-Isomer
D011985 Receptors, Serotonin Cell-surface proteins that bind SEROTONIN and trigger intracellular changes which influence the behavior of cells. Several types of serotonin receptors have been recognized which differ in their pharmacology, molecular biology, and mode of action. 5-HT Receptor,5-HT Receptors,5-Hydroxytryptamine Receptor,5-Hydroxytryptamine Receptors,Receptors, Tryptamine,Serotonin Receptor,Serotonin Receptors,Tryptamine Receptor,Tryptamine Receptors,Receptors, 5-HT,Receptors, 5-Hydroxytryptamine,5 HT Receptor,5 HT Receptors,5 Hydroxytryptamine Receptor,5 Hydroxytryptamine Receptors,Receptor, 5-HT,Receptor, 5-Hydroxytryptamine,Receptor, Serotonin,Receptor, Tryptamine,Receptors, 5 HT,Receptors, 5 Hydroxytryptamine
D004298 Dopamine One of the catecholamine NEUROTRANSMITTERS in the brain. It is derived from TYROSINE and is the precursor to NOREPINEPHRINE and EPINEPHRINE. Dopamine is a major transmitter in the extrapyramidal system of the brain, and important in regulating movement. A family of receptors (RECEPTORS, DOPAMINE) mediate its action. Hydroxytyramine,3,4-Dihydroxyphenethylamine,4-(2-Aminoethyl)-1,2-benzenediol,Dopamine Hydrochloride,Intropin,3,4 Dihydroxyphenethylamine,Hydrochloride, Dopamine
D000318 Adrenergic beta-Agonists Drugs that selectively bind to and activate beta-adrenergic receptors. Adrenergic beta-Receptor Agonists,beta-Adrenergic Agonists,beta-Adrenergic Receptor Agonists,Adrenergic beta-Agonist,Adrenergic beta-Receptor Agonist,Betamimetics,Receptor Agonists, beta-Adrenergic,Receptors Agonists, Adrenergic beta,beta-Adrenergic Agonist,beta-Adrenergic Receptor Agonist,Adrenergic beta Agonist,Adrenergic beta Agonists,Adrenergic beta Receptor Agonist,Adrenergic beta Receptor Agonists,Agonist, Adrenergic beta-Receptor,Agonist, beta-Adrenergic,Agonist, beta-Adrenergic Receptor,Agonists, Adrenergic beta-Receptor,Agonists, beta-Adrenergic,Agonists, beta-Adrenergic Receptor,Receptor Agonist, beta-Adrenergic,Receptor Agonists, beta Adrenergic,beta Adrenergic Agonist,beta Adrenergic Agonists,beta Adrenergic Receptor Agonist,beta Adrenergic Receptor Agonists,beta-Agonist, Adrenergic,beta-Agonists, Adrenergic,beta-Receptor Agonist, Adrenergic,beta-Receptor Agonists, Adrenergic
D000319 Adrenergic beta-Antagonists Drugs that bind to but do not activate beta-adrenergic receptors thereby blocking the actions of beta-adrenergic agonists. Adrenergic beta-antagonists are used for treatment of hypertension, cardiac arrhythmias, angina pectoris, glaucoma, migraine headaches, and anxiety. Adrenergic beta-Antagonist,Adrenergic beta-Receptor Blockader,Adrenergic beta-Receptor Blockaders,beta-Adrenergic Antagonist,beta-Adrenergic Blocker,beta-Adrenergic Blocking Agent,beta-Adrenergic Blocking Agents,beta-Adrenergic Receptor Blockader,beta-Adrenergic Receptor Blockaders,beta-Adrenoceptor Antagonist,beta-Blockers, Adrenergic,beta-Adrenergic Antagonists,beta-Adrenergic Blockers,beta-Adrenoceptor Antagonists,Adrenergic beta Antagonist,Adrenergic beta Antagonists,Adrenergic beta Receptor Blockader,Adrenergic beta Receptor Blockaders,Adrenergic beta-Blockers,Agent, beta-Adrenergic Blocking,Agents, beta-Adrenergic Blocking,Antagonist, beta-Adrenergic,Antagonist, beta-Adrenoceptor,Antagonists, beta-Adrenergic,Antagonists, beta-Adrenoceptor,Blockader, Adrenergic beta-Receptor,Blockader, beta-Adrenergic Receptor,Blockaders, Adrenergic beta-Receptor,Blockaders, beta-Adrenergic Receptor,Blocker, beta-Adrenergic,Blockers, beta-Adrenergic,Blocking Agent, beta-Adrenergic,Blocking Agents, beta-Adrenergic,Receptor Blockader, beta-Adrenergic,Receptor Blockaders, beta-Adrenergic,beta Adrenergic Antagonist,beta Adrenergic Antagonists,beta Adrenergic Blocker,beta Adrenergic Blockers,beta Adrenergic Blocking Agent,beta Adrenergic Blocking Agents,beta Adrenergic Receptor Blockader,beta Adrenergic Receptor Blockaders,beta Adrenoceptor Antagonist,beta Adrenoceptor Antagonists,beta Blockers, Adrenergic,beta-Antagonist, Adrenergic,beta-Antagonists, Adrenergic,beta-Receptor Blockader, Adrenergic,beta-Receptor Blockaders, Adrenergic
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D001058 Apomorphine A derivative of morphine that is a dopamine D2 agonist. It is a powerful emetic and has been used for that effect in acute poisoning. It has also been used in the diagnosis and treatment of parkinsonism, but its adverse effects limit its use. Apokinon,Apomorphin-Teclapharm,Apomorphine Chloride,Apomorphine Hydrochloride,Apomorphine Hydrochloride Anhydrous,Apomorphine Hydrochloride, Anhydrous,Apomorphine Hydrochloride, Hemihydrate,Britaject,Apomorphin Teclapharm
D001522 Behavior, Animal The observable response an animal makes to any situation. Autotomy Animal,Animal Behavior,Animal Behaviors

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