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Repeated adolescent 3,4-methylenedioxymethamphetamine (MDMA) exposure in rats attenuates the effects of a subsequent challenge with MDMA or a 5-hydroxytryptamine(1A) receptor agonist.
J Pharmacol Exp Ther 2006; 317(2):838-49JP

Abstract

Adolescent users of 3,4-methylenedioxymethamphetamine (MDMA, Ecstasy) may escalate their dose because of the development of tolerance. We examined the influence of intermittent adolescent MDMA exposure on the behavioral, physiological, and neurochemical responses to a subsequent MDMA "binge" or to a 5-hydroxytryptamine(1A) (5-HT(1A)) receptor challenge. Male Sprague-Dawley rats were given MDMA (10 mg/kg b.i.d.) or saline every 5th day on postnatal days (PDs) 35 to 60. One week later on PD 67, animals were challenged with either multiple doses of MDMA (four 5 or 10 mg/kg doses) or a single dose of the 5-HT(1A) agonist 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) (0.1 or 0.5 mg/kg). Adolescent MDMA exposure partially attenuated the hyperthermic effects of the PD 67 MDMA challenge, completely blocked the locomotor hypoactivity otherwise observed on the day after the challenge, and also prevented MDMA-induced serotonin neurotoxicity assessed on PD 74 by measuring regional [(3)H]citalopram binding to the serotonin transporter (SERT). Adolescent MDMA-treated animals also showed a partial attenuation of the serotonin syndrome but not the hypothermic response to the high dose of 8-OH-DPAT. However, there was no effect of MDMA administration on regional [(3)H]N-[2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl]-N-(2-pyridinyl)cyclohexanecarboxamide trihydrochloride (WAY-100635) binding to 5-HT(1A) receptors in the brain or spinal cord. These results suggest that chronic, intermittent MDMA exposure during adolescence induces neuroadaptive changes that can protect against the adverse consequences of a subsequent dose escalation. On the other hand, the same exposure pattern appears to produce a partial 5-HT(1A) receptor desensitization, which may negatively influence the therapeutic responses of chronic MDMA users treated with serotonergic agents for various affective or anxiety disorders.

Authors+Show Affiliations

Neuroscience and Behavior Program, University of Massachusetts, Amherst, MA 01003-7710, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

16434566

Citation

Piper, Brian J., et al. "Repeated Adolescent 3,4-methylenedioxymethamphetamine (MDMA) Exposure in Rats Attenuates the Effects of a Subsequent Challenge With MDMA or a 5-hydroxytryptamine(1A) Receptor Agonist." The Journal of Pharmacology and Experimental Therapeutics, vol. 317, no. 2, 2006, pp. 838-49.
Piper BJ, Vu HL, Safain MG, et al. Repeated adolescent 3,4-methylenedioxymethamphetamine (MDMA) exposure in rats attenuates the effects of a subsequent challenge with MDMA or a 5-hydroxytryptamine(1A) receptor agonist. J Pharmacol Exp Ther. 2006;317(2):838-49.
Piper, B. J., Vu, H. L., Safain, M. G., Oliver, A. J., & Meyer, J. S. (2006). Repeated adolescent 3,4-methylenedioxymethamphetamine (MDMA) exposure in rats attenuates the effects of a subsequent challenge with MDMA or a 5-hydroxytryptamine(1A) receptor agonist. The Journal of Pharmacology and Experimental Therapeutics, 317(2), pp. 838-49.
Piper BJ, et al. Repeated Adolescent 3,4-methylenedioxymethamphetamine (MDMA) Exposure in Rats Attenuates the Effects of a Subsequent Challenge With MDMA or a 5-hydroxytryptamine(1A) Receptor Agonist. J Pharmacol Exp Ther. 2006;317(2):838-49. PubMed PMID: 16434566.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Repeated adolescent 3,4-methylenedioxymethamphetamine (MDMA) exposure in rats attenuates the effects of a subsequent challenge with MDMA or a 5-hydroxytryptamine(1A) receptor agonist. AU - Piper,Brian J, AU - Vu,Huyen L, AU - Safain,Mina G, AU - Oliver,Andrew J, AU - Meyer,Jerrold S, Y1 - 2006/01/24/ PY - 2006/1/26/pubmed PY - 2006/6/10/medline PY - 2006/1/26/entrez SP - 838 EP - 49 JF - The Journal of pharmacology and experimental therapeutics JO - J. Pharmacol. Exp. Ther. VL - 317 IS - 2 N2 - Adolescent users of 3,4-methylenedioxymethamphetamine (MDMA, Ecstasy) may escalate their dose because of the development of tolerance. We examined the influence of intermittent adolescent MDMA exposure on the behavioral, physiological, and neurochemical responses to a subsequent MDMA "binge" or to a 5-hydroxytryptamine(1A) (5-HT(1A)) receptor challenge. Male Sprague-Dawley rats were given MDMA (10 mg/kg b.i.d.) or saline every 5th day on postnatal days (PDs) 35 to 60. One week later on PD 67, animals were challenged with either multiple doses of MDMA (four 5 or 10 mg/kg doses) or a single dose of the 5-HT(1A) agonist 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) (0.1 or 0.5 mg/kg). Adolescent MDMA exposure partially attenuated the hyperthermic effects of the PD 67 MDMA challenge, completely blocked the locomotor hypoactivity otherwise observed on the day after the challenge, and also prevented MDMA-induced serotonin neurotoxicity assessed on PD 74 by measuring regional [(3)H]citalopram binding to the serotonin transporter (SERT). Adolescent MDMA-treated animals also showed a partial attenuation of the serotonin syndrome but not the hypothermic response to the high dose of 8-OH-DPAT. However, there was no effect of MDMA administration on regional [(3)H]N-[2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl]-N-(2-pyridinyl)cyclohexanecarboxamide trihydrochloride (WAY-100635) binding to 5-HT(1A) receptors in the brain or spinal cord. These results suggest that chronic, intermittent MDMA exposure during adolescence induces neuroadaptive changes that can protect against the adverse consequences of a subsequent dose escalation. On the other hand, the same exposure pattern appears to produce a partial 5-HT(1A) receptor desensitization, which may negatively influence the therapeutic responses of chronic MDMA users treated with serotonergic agents for various affective or anxiety disorders. SN - 0022-3565 UR - https://www.unboundmedicine.com/medline/citation/16434566/Repeated_adolescent_34_methylenedioxymethamphetamine__MDMA__exposure_in_rats_attenuates_the_effects_of_a_subsequent_challenge_with_MDMA_or_a_5_hydroxytryptamine_1A__receptor_agonist_ L2 - http://jpet.aspetjournals.org/cgi/pmidlookup?view=long&pmid=16434566 DB - PRIME DP - Unbound Medicine ER -