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Relationship between anorexia and loss of serotonin uptake sites in brain of mice and rats receiving d-norfenfluramine or d-fenfluramine.
Pharmacol Biochem Behav. 2004 Mar; 77(3):541-6.PB

Abstract

Previously, we have shown that repeated administration of d-fenfluramine (D-F) to rats is associated with development of tolerance to the initial anorexia, but that in mice no such tolerance seems to occur. In the first study, we show that chronic administration of neither d-norfenfluramine (D-NF; the principal metabolite of D-F) nor the serotonin (5-HT) 2C receptor agonist m-chlorophenyl-piperazine (mCPP) is associated with the development of anorectic tolerance tested using a dessert protocol. However, compared with mice receiving these drugs for the first time, both of these chronic treatments were associated with a significant attenuation of Fos immunoreactivity (Fos-ir) in several brain regions, including bed nucleus of the stria terminalis, paraventricular hypothalamus, and central nucleus of amygdala. This attenuation is similar to that described previously in rats. Because loss of efficacy of these agents could be related to loss of 5-HT transporter (5-HTT) sites, their presumptive primary mode of action, in the final study we determined the effect of various, low-dose regimens of D-F and D-NF on 5-HT uptake in frontal cortex of mice and rats. We show in mice that D-F causes a greater loss of 5-HT uptake than D-NF, and that at the lowest dose regimen used uptake was unaffected in rats but was reduced in mice. The data are discussed in terms of the species difference in behavioral tolerance and differences in neurochemical profile of D-F and D-NF.

Authors+Show Affiliations

Department of Psychology, University of Florida, POB 112250, Gainesville, FL 32611-2250, USA. nrowland@ufl.eduNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Comparative Study
Journal Article

Language

eng

PubMed ID

15006465

Citation

Rowland, Neil E., et al. "Relationship Between Anorexia and Loss of Serotonin Uptake Sites in Brain of Mice and Rats Receiving D-norfenfluramine or D-fenfluramine." Pharmacology, Biochemistry, and Behavior, vol. 77, no. 3, 2004, pp. 541-6.
Rowland NE, Rokadia S, Green DJ, et al. Relationship between anorexia and loss of serotonin uptake sites in brain of mice and rats receiving d-norfenfluramine or d-fenfluramine. Pharmacol Biochem Behav. 2004;77(3):541-6.
Rowland, N. E., Rokadia, S., Green, D. J., & Robertson, K. (2004). Relationship between anorexia and loss of serotonin uptake sites in brain of mice and rats receiving d-norfenfluramine or d-fenfluramine. Pharmacology, Biochemistry, and Behavior, 77(3), 541-6.
Rowland NE, et al. Relationship Between Anorexia and Loss of Serotonin Uptake Sites in Brain of Mice and Rats Receiving D-norfenfluramine or D-fenfluramine. Pharmacol Biochem Behav. 2004;77(3):541-6. PubMed PMID: 15006465.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Relationship between anorexia and loss of serotonin uptake sites in brain of mice and rats receiving d-norfenfluramine or d-fenfluramine. AU - Rowland,Neil E, AU - Rokadia,Sana, AU - Green,D Joy, AU - Robertson,Kimberly, PY - 2003/08/08/received PY - 2003/12/11/revised PY - 2003/12/11/accepted PY - 2004/3/10/pubmed PY - 2004/10/23/medline PY - 2004/3/10/entrez SP - 541 EP - 6 JF - Pharmacology, biochemistry, and behavior JO - Pharmacol Biochem Behav VL - 77 IS - 3 N2 - Previously, we have shown that repeated administration of d-fenfluramine (D-F) to rats is associated with development of tolerance to the initial anorexia, but that in mice no such tolerance seems to occur. In the first study, we show that chronic administration of neither d-norfenfluramine (D-NF; the principal metabolite of D-F) nor the serotonin (5-HT) 2C receptor agonist m-chlorophenyl-piperazine (mCPP) is associated with the development of anorectic tolerance tested using a dessert protocol. However, compared with mice receiving these drugs for the first time, both of these chronic treatments were associated with a significant attenuation of Fos immunoreactivity (Fos-ir) in several brain regions, including bed nucleus of the stria terminalis, paraventricular hypothalamus, and central nucleus of amygdala. This attenuation is similar to that described previously in rats. Because loss of efficacy of these agents could be related to loss of 5-HT transporter (5-HTT) sites, their presumptive primary mode of action, in the final study we determined the effect of various, low-dose regimens of D-F and D-NF on 5-HT uptake in frontal cortex of mice and rats. We show in mice that D-F causes a greater loss of 5-HT uptake than D-NF, and that at the lowest dose regimen used uptake was unaffected in rats but was reduced in mice. The data are discussed in terms of the species difference in behavioral tolerance and differences in neurochemical profile of D-F and D-NF. SN - 0091-3057 UR - https://www.unboundmedicine.com/medline/citation/15006465/Relationship_between_anorexia_and_loss_of_serotonin_uptake_sites_in_brain_of_mice_and_rats_receiving_d_norfenfluramine_or_d_fenfluramine_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0091305703003721 DB - PRIME DP - Unbound Medicine ER -