8-OH-DPAT acts on both 5-HT1A and 5-HT7 receptors to induce hypothermia in rodents

Department of Molecular Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA.
European Journal of Pharmacology (Impact Factor: 2.68). 04/2004; 487(1-3):125-32. DOI: 10.1016/j.ejphar.2004.01.031
Source: PubMed

ABSTRACT Studies using selective drugs and knockout mice have demonstrated that the 5-HT(7) receptor plays an instrumental role in serotonin-induced hypothermia. There is also evidence supporting an involvement of the 5-HT(1A) receptor, although mainly from studies using 8-hydroxy-2(di-n-propylamino)tetralin (8-OH-DPAT), a 5-HT(1A/7) receptor agonist. Here we studied the effects of 8-OH-DPAT and selective antagonists for the 5-HT(1A) and 5-HT(7) receptors on body temperature in rats, wild-type (5-HT(7)(+/+)) mice and knockout (5-HT(7)(-/-)) mice. At lower doses (0.3-0.6 mg/kg, i.p.), 8-OH-DPAT decreased body temperature in 5-HT(7)(+/+) mice but not in 5-HT(7)(-/-) mice. At a higher dose (1 mg/kg, i.p.) 8-OH-DPAT induced hypothermia in both 5-HT(7)(-/-) and 5-HT(7)(+/+) mice. The 5-HT(1A) receptor antagonist (S)-N-tert-butyl-3-(4-(2-methoxyphenyl)piperazine-1-yl)-2-phenylpropanamide (WAY-100135) (10 mg/kg, i.p.) inhibited the effect of 8-OH-DPAT at all doses in rats and mice. In 5-HT(7)(+/+) mice the selective 5-HT(7) receptor antagonist (R)-3-(2-(2-(4-methylpiperidin-1-yl)-ethyl)pyrrolidine-1-sulfonyl)phenol (SB-269970) (10 mg/kg, i.p.) fully inhibited the hypothermia induced by 0.3 mg/kg 8-OH-DPAT, but not that of higher doses. In rats, SB-269970 caused a 60% inhibition of the hypothermia induced by 0.3 mg/kg 8-OH-DPAT. Thus, both 5-HT(7) and 5-HT(1A) receptors are involved in a complex manner in thermoregulation, with the 5-HT(7) receptor being more important at lower, possibly more physiological, concentrations.

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    • "One of them, 8-OH-DPAT, is an aminotetralin derivative which was developed in the 1980s and was one of the first major 5-HT 1A receptor agonists to be discovered [10]. 8-OH-DPAT has been extensively used in pharmacological studies characterizing 5-HT 1A [35], although it was later found to act as a 5-HT 7 receptor agonist [36]. Other compounds acting on 5-HT 1A receptors exhibit similar complex pharmacological profiles. "
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    ABSTRACT: Serotonin and its various receptors are involved in numerous brain functions and neuropsychiatric disorders. The 5-HT1A family is the best characterized subtype of the fourteen currently known 5-HT receptors. The 5-HT1A receptor is closely involved in the pathogenesis of anxiety, depression, epilepsy and eating disorders and therefore is an important target for drug therapy. The development in the 1980s of molecules specifically targeting this receptor was followed by the rapid development of corresponding PET neuroimaging. Because this receptor represents a crucial target in neuroscience, a large number of radioligands have been developed by academic and industry centers for visualization and quantification, first in living animals and ultimately in humans. After a brief account of some of the structural and functional characteristics of brain 5-HT1A receptors, this review focuses on the main lines of evolution opened up by preclinical and clinical 5-HT1A PET radiopharmaceuticals, illustrating the potential value of PET for clinical research and drug development.
    Current Medicinal Chemistry 08/2013; DOI:10.2174/09298673113209990215 · 3.85 Impact Factor
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    • "In addition, (±)-8-OH-DPAT effectively alleviated the fluoxetine enhancement of haloperidol-induced EPS. Although (±)- 8-OH-DPAT has an affinity not only for 5-HT 1A receptors, but also for 5-HT 7 receptors (Hedlund et al., 2004), the reversal of the fluoxetine enhancement of EPS with (±)-8-OH-DPAT was abolished by the selective 5-HT 1A antagonist (S)-WAY-100135. The dosage (5–20 mg/kg) of fluoxetine used herein was in a range that reportedly inhibits 5-HT reuptake and increases the extracellular level of 5-HT (Paez and Leibowitz, 1993; Perry and Fuller, 1992). "
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    Progress in Neuro-Psychopharmacology and Biological Psychiatry 07/2013; 46. DOI:10.1016/j.pnpbp.2013.06.016 · 4.03 Impact Factor
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    • "This probe was lubricated with vaseline and inserted 2 cm into the rectum. Temperature recordings were made 20 s following insertion of the probe, as previously described [27] [28]. "
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    Advances in Pharmacological Sciences 06/2012; 2012:312041. DOI:10.1155/2012/312041
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