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1-(m-chlorophenyl)piperazine (mCPP) dissociates in vivo serotonin release from long-term serotonin depletion in rat brain.
Neuropsychopharmacology. 2001 May; 24(5):492-501.N

Abstract

Serotonin (5-HT) releasing agents such as d-fenfluramine are known to cause long-term depletion of forebrain 5-HT in animals, but the mechanism of this effect is unknown. In the present study, we examined the relationship between drug-induced 5-HT release and long-term 5-HT depletion in rat brain. The 5-HT-releasing actions of d-fenfluramine and a non-amphetamine 5-HT drug, 1-(m-chlorophenyl)piperazine (mCPP), were compared using in vivo microdialysis in the nucleus accumbens. The ability of d-fenfluramine and mCPP to interact with 5-HT transporters was tested using in vitro assays for [3H]5-HT uptake and radioligand binding. Local infusion of d-fenfluramine or mCPP (1-100 microM) increased extracellular 5-HT, with elevations in dopamine occurring at high doses. Intravenous injection of either drug (1-10 micromol/kg) produced dose-related increases in 5-HT without affecting dopamine. d-Fenfluramine and mCPP exhibited similar potency in their ability to stimulate 5-HT efflux in vivo and interact with 5-HT transporters in vitro. When rats received high-dose d-fenfluramine or mCPP (10 or 30 micromol/kg, i.p., every 2 h, 4 doses), only d-fenfluramine-treated rats displayed long-term 5-HT depletions. Thus, mCPP is a 5-HT releaser that does not appear to cause 5-HT depletion. Our data support the notion that 5-HT release per se may not be sufficient to produce the long-term 5-HT deficits associated with d-fenfluramine and other amphetamines.

Authors+Show Affiliations

Clinical Psychopharmacology Section, Intramural Research Program, National Institute on Drug Abuse, National Institutes of Health, Baltimore, MD 21224, USA.No affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

11282249

Citation

Baumann, M H., et al. "1-(m-chlorophenyl)piperazine (mCPP) Dissociates in Vivo Serotonin Release From Long-term Serotonin Depletion in Rat Brain." Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology, vol. 24, no. 5, 2001, pp. 492-501.
Baumann MH, Ayestas MA, Dersch CM, et al. 1-(m-chlorophenyl)piperazine (mCPP) dissociates in vivo serotonin release from long-term serotonin depletion in rat brain. Neuropsychopharmacology. 2001;24(5):492-501.
Baumann, M. H., Ayestas, M. A., Dersch, C. M., & Rothman, R. B. (2001). 1-(m-chlorophenyl)piperazine (mCPP) dissociates in vivo serotonin release from long-term serotonin depletion in rat brain. Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology, 24(5), 492-501.
Baumann MH, et al. 1-(m-chlorophenyl)piperazine (mCPP) Dissociates in Vivo Serotonin Release From Long-term Serotonin Depletion in Rat Brain. Neuropsychopharmacology. 2001;24(5):492-501. PubMed PMID: 11282249.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - 1-(m-chlorophenyl)piperazine (mCPP) dissociates in vivo serotonin release from long-term serotonin depletion in rat brain. AU - Baumann,M H, AU - Ayestas,M A, AU - Dersch,C M, AU - Rothman,R B, PY - 2001/4/3/pubmed PY - 2001/7/13/medline PY - 2001/4/3/entrez SP - 492 EP - 501 JF - Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology JO - Neuropsychopharmacology VL - 24 IS - 5 N2 - Serotonin (5-HT) releasing agents such as d-fenfluramine are known to cause long-term depletion of forebrain 5-HT in animals, but the mechanism of this effect is unknown. In the present study, we examined the relationship between drug-induced 5-HT release and long-term 5-HT depletion in rat brain. The 5-HT-releasing actions of d-fenfluramine and a non-amphetamine 5-HT drug, 1-(m-chlorophenyl)piperazine (mCPP), were compared using in vivo microdialysis in the nucleus accumbens. The ability of d-fenfluramine and mCPP to interact with 5-HT transporters was tested using in vitro assays for [3H]5-HT uptake and radioligand binding. Local infusion of d-fenfluramine or mCPP (1-100 microM) increased extracellular 5-HT, with elevations in dopamine occurring at high doses. Intravenous injection of either drug (1-10 micromol/kg) produced dose-related increases in 5-HT without affecting dopamine. d-Fenfluramine and mCPP exhibited similar potency in their ability to stimulate 5-HT efflux in vivo and interact with 5-HT transporters in vitro. When rats received high-dose d-fenfluramine or mCPP (10 or 30 micromol/kg, i.p., every 2 h, 4 doses), only d-fenfluramine-treated rats displayed long-term 5-HT depletions. Thus, mCPP is a 5-HT releaser that does not appear to cause 5-HT depletion. Our data support the notion that 5-HT release per se may not be sufficient to produce the long-term 5-HT deficits associated with d-fenfluramine and other amphetamines. SN - 0893-133X UR - https://www.unboundmedicine.com/medline/citation/11282249/1__m_chlorophenyl_piperazine__mCPP__dissociates_in_vivo_serotonin_release_from_long_term_serotonin_depletion_in_rat_brain_ DB - PRIME DP - Unbound Medicine ER -