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Reduced sensitivity to MDMA-induced facilitation of social behaviour in MDMA pre-exposed rats.
Prog Neuropsychopharmacol Biol Psychiatry. 2008 May 15; 32(4):1013-21.PN

Abstract

The acute effects of the party drug 3,4-methylenedioxymethamphetamine (MDMA, "Ecstasy") in humans include feelings of love, closeness towards other people and an increased acceptance of others views and feelings. Some evidence suggests that regular MDMA users develop a subsensitivity to the positive effects of the drug and escalate their intake of the drug over time as a result. The current study investigated whether brief exposure to relatively high doses of MDMA in rats produces a subsequent attenuation in the ability of MDMA to enhance social interaction. Male Wistar rats were exposed to either MDMA (4 x 5 mg/kg over 4 h) or vehicle on two consecutive days. Twelve weeks later, MDMA pre-exposed rats displayed a significantly shorter period of time spent in social interaction than controls when tested in the drug-free state. MDMA pre-exposed rats also showed a blunted prosocial response to MDMA (2.5 mg/kg) relative to controls. This difference was overcome by increasing the MDMA dose to 5 mg/kg. The 5-HT(1A) agonist 8-OH-DPAT (250 microg/kg but not 125 microg/kg) increased social interaction and this effect did not differ in MDMA and vehicle pre-exposed rats. HPLC analysis showed a small but significant depletion of prefrontal 5-HT and 5-HIAA in MDMA pre-exposed rats. Prefrontal 5-HIAA concentrations were also reduced in the subset of vehicle and MDMA pre-exposed rats that received additional testing with MDMA. These results indicate that treatment with MDMA not only causes lasting reductions in social interaction in rats but causes an attenuation of the prosocial effects of subsequent MDMA administration. The lack of a differential response to 8-OH-DPAT agrees with other findings that the 5-HT(1A) receptor system remains functionally intact following MDMA pre-exposure and suggests that other neuroadaptations may underlie the lasting social deficits caused by MDMA.

Authors+Show Affiliations

School of Psychology, University of Sydney, A18, Sydney, NSW 2006, Australia.No affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

18302974

Citation

Thompson, Murray R., et al. "Reduced Sensitivity to MDMA-induced Facilitation of Social Behaviour in MDMA Pre-exposed Rats." Progress in Neuro-psychopharmacology & Biological Psychiatry, vol. 32, no. 4, 2008, pp. 1013-21.
Thompson MR, Callaghan PD, Hunt GE, et al. Reduced sensitivity to MDMA-induced facilitation of social behaviour in MDMA pre-exposed rats. Prog Neuropsychopharmacol Biol Psychiatry. 2008;32(4):1013-21.
Thompson, M. R., Callaghan, P. D., Hunt, G. E., & McGregor, I. S. (2008). Reduced sensitivity to MDMA-induced facilitation of social behaviour in MDMA pre-exposed rats. Progress in Neuro-psychopharmacology & Biological Psychiatry, 32(4), 1013-21. https://doi.org/10.1016/j.pnpbp.2008.01.014
Thompson MR, et al. Reduced Sensitivity to MDMA-induced Facilitation of Social Behaviour in MDMA Pre-exposed Rats. Prog Neuropsychopharmacol Biol Psychiatry. 2008 May 15;32(4):1013-21. PubMed PMID: 18302974.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Reduced sensitivity to MDMA-induced facilitation of social behaviour in MDMA pre-exposed rats. AU - Thompson,Murray R, AU - Callaghan,Paul D, AU - Hunt,Glenn E, AU - McGregor,Iain S, Y1 - 2008/02/04/ PY - 2007/08/05/received PY - 2008/01/24/revised PY - 2008/01/24/accepted PY - 2008/2/28/pubmed PY - 2008/7/23/medline PY - 2008/2/28/entrez SP - 1013 EP - 21 JF - Progress in neuro-psychopharmacology & biological psychiatry JO - Prog. Neuropsychopharmacol. Biol. Psychiatry VL - 32 IS - 4 N2 - The acute effects of the party drug 3,4-methylenedioxymethamphetamine (MDMA, "Ecstasy") in humans include feelings of love, closeness towards other people and an increased acceptance of others views and feelings. Some evidence suggests that regular MDMA users develop a subsensitivity to the positive effects of the drug and escalate their intake of the drug over time as a result. The current study investigated whether brief exposure to relatively high doses of MDMA in rats produces a subsequent attenuation in the ability of MDMA to enhance social interaction. Male Wistar rats were exposed to either MDMA (4 x 5 mg/kg over 4 h) or vehicle on two consecutive days. Twelve weeks later, MDMA pre-exposed rats displayed a significantly shorter period of time spent in social interaction than controls when tested in the drug-free state. MDMA pre-exposed rats also showed a blunted prosocial response to MDMA (2.5 mg/kg) relative to controls. This difference was overcome by increasing the MDMA dose to 5 mg/kg. The 5-HT(1A) agonist 8-OH-DPAT (250 microg/kg but not 125 microg/kg) increased social interaction and this effect did not differ in MDMA and vehicle pre-exposed rats. HPLC analysis showed a small but significant depletion of prefrontal 5-HT and 5-HIAA in MDMA pre-exposed rats. Prefrontal 5-HIAA concentrations were also reduced in the subset of vehicle and MDMA pre-exposed rats that received additional testing with MDMA. These results indicate that treatment with MDMA not only causes lasting reductions in social interaction in rats but causes an attenuation of the prosocial effects of subsequent MDMA administration. The lack of a differential response to 8-OH-DPAT agrees with other findings that the 5-HT(1A) receptor system remains functionally intact following MDMA pre-exposure and suggests that other neuroadaptations may underlie the lasting social deficits caused by MDMA. SN - 0278-5846 UR - https://www.unboundmedicine.com/medline/citation/18302974/Reduced_sensitivity_to_MDMA_induced_facilitation_of_social_behaviour_in_MDMA_pre_exposed_rats_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0278-5846(08)00044-4 DB - PRIME DP - Unbound Medicine ER -