5-HT1A and 5-HT2 receptors mediate discrete behaviors in the Mongolian gerbil. 1992

A S Eison, and R N Wright
CNS Special Projects, Bristol-Myers Squibb Company, Wallingford, CT 06492.

Although the ability of agonists at specific serotonin (5-HT) receptor subtypes to induce distinct behaviors has been well documented in the rat, similar studies have not been reported in the Mongolian gerbil. We have found that the 5-HT1A/5-HT2 agonist 5-methoxy,N-N dimethyltryptamine (5-MeODMT) (0.5-8 mg/kg, SC), the specific 5-HT1A agonist 8-hydroxy(di-n-propylamino)tetralin (8-OH-DPAT) (0.125-16 mg/kg, SC), and the 5-HT precursor L-5-hydroxytryptophan (L-5-HTP) (100-250 mg/kg, SC) all elicit a 5-HT syndrome in the gerbil. This syndrome, analogous to the 5-HT syndrome in the rat, consists of reciprocal forepaw treading (RFT), hindleg abduction (HA), body tremors (BT), and Straub tail (ST). The putative 5-HT1A antagonist NAN-190 (0.25-8 mg/kg, SC) when dosed 15 min prior to either 5-MeODMT (4 mg/kg, SC) or 8-OH-DPAT (16 mg/kg, SC) blocked both RFT and HA in a dose-dependent manner, suggesting these 5-HT syndrome behaviors are mediated via 5-HT1A receptor activation. We also identified a unique, dose-responsive behavior in the gerbil, induced selectively by 5-HT1A agonists such as quipazine (2-16 mg/kg, SC) and (+-)-1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI) (0.125-8 mg/kg, SC). This reciprocal hindleg body scratch (RHBS) behavior is dose dependently inhibited by pretreatment with the selective 5-HT2 antagonist ritanserin (0.0125-0.2 mg/kg, SC). RHBS behavior is also potently inhibited by pretreatment with the selective 5-HT1A agonist 8-OH-DPAT (0.005-0.04 mg/kg, SC), demonstrating a 5-HT1A/5-HT2 receptor subtype interaction.(ABSTRACT TRUNCATED AT 250 WORDS)

UI MeSH Term Description Entries
D008297 Male Males
D008732 Methoxydimethyltryptamines Compounds that contain the biogenic monoamine tryptamine and are substituted with one methoxy group and two methyl groups. Members of this group include several potent serotonergic hallucinogens found in several unrelated plants, skins of certain toads, and in mammalian brains. They are possibly involved in the etiology of schizophrenia. Methylbufotenin,5-Methoxy-N,N-Dimethyltryptamine,Methoxydimethyltryptamine,N,N-Dimethyl-5-Methoxytryptamine,5 Methoxy N,N Dimethyltryptamine,N,N Dimethyl 5 Methoxytryptamine
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
D004305 Dose-Response Relationship, Drug The relationship between the dose of an administered drug and the response of the organism to the drug. Dose Response Relationship, Drug,Dose-Response Relationships, Drug,Drug Dose-Response Relationship,Drug Dose-Response Relationships,Relationship, Drug Dose-Response,Relationships, Drug Dose-Response
D004347 Drug Interactions The action of a drug that may affect the activity, metabolism, or toxicity of another drug. Drug Interaction,Interaction, Drug,Interactions, Drug
D005849 Gerbillinae A subfamily of the Muridae consisting of several genera including Gerbillus, Rhombomys, Tatera, Meriones, and Psammomys. Gerbils,Jird,Meriones,Psammomys,Rats, Sand,Gerbil,Jirds,Merione,Rat, Sand,Sand Rat,Sand Rats
D006916 5-Hydroxytryptophan The immediate precursor in the biosynthesis of SEROTONIN from tryptophan. It is used as an antiepileptic and antidepressant. 5-HTP,Hydroxytryptophan,Oxitriptan,Oxytryptophan,Tryptophan, 5-Hydroxy-,5 Hydroxytryptophan,5-Hydroxy- Tryptophan,Tryptophan, 5 Hydroxy
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
D001522 Behavior, Animal The observable response an animal makes to any situation. Autotomy Animal,Animal Behavior,Animal Behaviors
D012701 Serotonin A biochemical messenger and regulator, synthesized from the essential amino acid L-TRYPTOPHAN. In humans it is found primarily in the central nervous system, gastrointestinal tract, and blood platelets. Serotonin mediates several important physiological functions including neurotransmission, gastrointestinal motility, hemostasis, and cardiovascular integrity. Multiple receptor families (RECEPTORS, SEROTONIN) explain the broad physiological actions and distribution of this biochemical mediator. 5-HT,5-Hydroxytryptamine,3-(2-Aminoethyl)-1H-indol-5-ol,Enteramine,Hippophaine,Hydroxytryptamine,5 Hydroxytryptamine

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