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Weekly gamma-hydroxybutyrate exposure sensitizes locomotor hyperactivity to low-dose 3,4-methylenedioxymethamphetamine in rats.
Neuropsychobiology. 2009; 60(3-4):195-203.N

Abstract

Users of the popular party drug 3,4-methylenedioxymethamphetamine (MDMA) sometimes report combining MDMA with gamma-hydroxybutyrate (GHB) to enhance the pleasurable effects of both drugs. However, very few studies have examined the influences of this drug combination. The present study investigated the development of locomotor sensitization in laboratory rats given 7 once-weekly exposures to either MDMA, GHB or their combination (MDMA/GHB). The drugs were administered at a high ambient temperature (28 degrees C) to mimic nightclub conditions. MDMA (5 mg/kg), given once weekly, produced a progressively greater locomotor and hyperthermic response over time. In contrast, GHB (500 mg/kg) administered weekly produced consistent low levels of locomotor activity and few changes in body temperature. Rats receiving the mixture of MDMA (5 mg/kg) and GHB (500 mg/kg) showed asymptotic levels of sensitized locomotor activity similar to those seen in rats given MDMA alone, but the development of locomotor sensitization was delayed by coadministered GHB. GHB also delayed the development of MDMA-induced hyperthermia. After a washout period of 5 weeks, rats pre-exposed to MDMA, GHB and MDMA/GHB showed no hyperactivity when tested drug-free in the context in which they had previously received drugs, but displayed a sensitized locomotor response to a low challenge dose of MDMA (2.5 mg/kg). The response to a low dose of methamphetamine (0.5 mg/kg) did not differ among groups. Neurochemical analysis using high-performance liquid chromatography revealed few lasting changes in serotonin, dopamine or their metabolites in the striatum or prefrontal cortex of MDMA- or GHB-pre-exposed rats. These results indicate that GHB modulates the locomotor and hyperthermic response to acute MDMA and that pre-exposure to GHB can sensitize the locomotor response to low doses of MDMA.

Authors+Show Affiliations

School of Psychology, University of Sydney, Concord Hospital, Sydney, N.S.W. 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

19893336

Citation

van Nieuwenhuijzen, P S., et al. "Weekly Gamma-hydroxybutyrate Exposure Sensitizes Locomotor Hyperactivity to Low-dose 3,4-methylenedioxymethamphetamine in Rats." Neuropsychobiology, vol. 60, no. 3-4, 2009, pp. 195-203.
van Nieuwenhuijzen PS, Li KM, Hunt GE, et al. Weekly gamma-hydroxybutyrate exposure sensitizes locomotor hyperactivity to low-dose 3,4-methylenedioxymethamphetamine in rats. Neuropsychobiology. 2009;60(3-4):195-203.
van Nieuwenhuijzen, P. S., Li, K. M., Hunt, G. E., & McGregor, I. S. (2009). Weekly gamma-hydroxybutyrate exposure sensitizes locomotor hyperactivity to low-dose 3,4-methylenedioxymethamphetamine in rats. Neuropsychobiology, 60(3-4), 195-203. https://doi.org/10.1159/000253555
van Nieuwenhuijzen PS, et al. Weekly Gamma-hydroxybutyrate Exposure Sensitizes Locomotor Hyperactivity to Low-dose 3,4-methylenedioxymethamphetamine in Rats. Neuropsychobiology. 2009;60(3-4):195-203. PubMed PMID: 19893336.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Weekly gamma-hydroxybutyrate exposure sensitizes locomotor hyperactivity to low-dose 3,4-methylenedioxymethamphetamine in rats. AU - van Nieuwenhuijzen,P S, AU - Li,K M, AU - Hunt,G E, AU - McGregor,I S, Y1 - 2009/11/05/ PY - 2009/11/7/entrez PY - 2009/11/7/pubmed PY - 2010/1/30/medline SP - 195 EP - 203 JF - Neuropsychobiology JO - Neuropsychobiology VL - 60 IS - 3-4 N2 - Users of the popular party drug 3,4-methylenedioxymethamphetamine (MDMA) sometimes report combining MDMA with gamma-hydroxybutyrate (GHB) to enhance the pleasurable effects of both drugs. However, very few studies have examined the influences of this drug combination. The present study investigated the development of locomotor sensitization in laboratory rats given 7 once-weekly exposures to either MDMA, GHB or their combination (MDMA/GHB). The drugs were administered at a high ambient temperature (28 degrees C) to mimic nightclub conditions. MDMA (5 mg/kg), given once weekly, produced a progressively greater locomotor and hyperthermic response over time. In contrast, GHB (500 mg/kg) administered weekly produced consistent low levels of locomotor activity and few changes in body temperature. Rats receiving the mixture of MDMA (5 mg/kg) and GHB (500 mg/kg) showed asymptotic levels of sensitized locomotor activity similar to those seen in rats given MDMA alone, but the development of locomotor sensitization was delayed by coadministered GHB. GHB also delayed the development of MDMA-induced hyperthermia. After a washout period of 5 weeks, rats pre-exposed to MDMA, GHB and MDMA/GHB showed no hyperactivity when tested drug-free in the context in which they had previously received drugs, but displayed a sensitized locomotor response to a low challenge dose of MDMA (2.5 mg/kg). The response to a low dose of methamphetamine (0.5 mg/kg) did not differ among groups. Neurochemical analysis using high-performance liquid chromatography revealed few lasting changes in serotonin, dopamine or their metabolites in the striatum or prefrontal cortex of MDMA- or GHB-pre-exposed rats. These results indicate that GHB modulates the locomotor and hyperthermic response to acute MDMA and that pre-exposure to GHB can sensitize the locomotor response to low doses of MDMA. SN - 1423-0224 UR - https://www.unboundmedicine.com/medline/citation/19893336/Weekly_gamma_hydroxybutyrate_exposure_sensitizes_locomotor_hyperactivity_to_low_dose_34_methylenedioxymethamphetamine_in_rats_ L2 - https://www.karger.com?DOI=10.1159/000253555 DB - PRIME DP - Unbound Medicine ER -