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Chronic administration of THC prevents the behavioral effects of intermittent adolescent MDMA administration and attenuates MDMA-induced hyperthermia and neurotoxicity in rats.
Neuropharmacology 2011; 61(8):1183-92N

Abstract

Most recreational users of 3, 4-methylenedioxymethamphetamine (MDMA or "ecstasy") also take cannabis, in part because cannabis can reduce the dysphoric symptoms of the ecstasy come-down such as agitation and insomnia. Although previous animal studies have examined the acute effects of co-administering MDMA and Δ(9)-tetrahydrocannabinol (THC), which is the major psychoactive ingredient in cannabis, research on chronic exposure to this drug combination is lacking. Therefore, the present study was conducted to investigate the effects of chronic adolescent administration of both THC and MDMA on behavior and on regional serotonin transporter (SERT) binding and serotonin (5-HT) concentrations as indices of serotonergic system integrity. Male Sprague-Dawley rats were divided into four drug administration groups: (1) MDMA alone, (2) THC alone, (3) MDMA plus THC, and (4) vehicle controls. MDMA (2 × 10 mg/kg × 4 h) was administered every fifth day from postnatal day (PD) 35 to 60 to simulate intermittent recreational ecstasy use, whereas THC (5mg/kg) was given once daily over the same time period to simulate heavy cannabis use. THC unexpectedly produced a modest hyperthermic effect when administered alone, but in animals co-treated with both THC and MDMA, there was an attenuation of MDMA-induced hyperthermia on dosing days. Subsequent testing conducted after a drug washout period revealed that THC reduced MDMA-related behavioral changes in the emergence and social interaction tests of anxiety-like behavior and also blunted the MDMA-induced decrease in exploratory behavior in the hole-board test. THC additionally attenuated MDMA -induced decreases in 5-HT levels and in SERT binding in the frontal cortex, parietal cortex, and striatum, but not in the hippocampus. These results suggest that chronic co-administration of THC during adolescence can provide some protection against various adverse physiological, behavioral, and neurochemical effects produced by MDMA.

Authors+Show Affiliations

Neuroscience and Behavior Program, University of Massachusetts, Amherst, MA 01003, USA. yshen@cns.umass.eduNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural

Language

eng

PubMed ID

21763331

Citation

Shen, Erica Y., et al. "Chronic Administration of THC Prevents the Behavioral Effects of Intermittent Adolescent MDMA Administration and Attenuates MDMA-induced Hyperthermia and Neurotoxicity in Rats." Neuropharmacology, vol. 61, no. 8, 2011, pp. 1183-92.
Shen EY, Ali SF, Meyer JS. Chronic administration of THC prevents the behavioral effects of intermittent adolescent MDMA administration and attenuates MDMA-induced hyperthermia and neurotoxicity in rats. Neuropharmacology. 2011;61(8):1183-92.
Shen, E. Y., Ali, S. F., & Meyer, J. S. (2011). Chronic administration of THC prevents the behavioral effects of intermittent adolescent MDMA administration and attenuates MDMA-induced hyperthermia and neurotoxicity in rats. Neuropharmacology, 61(8), pp. 1183-92. doi:10.1016/j.neuropharm.2011.07.002.
Shen EY, Ali SF, Meyer JS. Chronic Administration of THC Prevents the Behavioral Effects of Intermittent Adolescent MDMA Administration and Attenuates MDMA-induced Hyperthermia and Neurotoxicity in Rats. Neuropharmacology. 2011;61(8):1183-92. PubMed PMID: 21763331.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Chronic administration of THC prevents the behavioral effects of intermittent adolescent MDMA administration and attenuates MDMA-induced hyperthermia and neurotoxicity in rats. AU - Shen,Erica Y, AU - Ali,Syed F, AU - Meyer,Jerrold S, Y1 - 2011/07/13/ PY - 2011/01/16/received PY - 2011/06/27/revised PY - 2011/07/01/accepted PY - 2011/7/19/entrez PY - 2011/7/19/pubmed PY - 2012/8/2/medline SP - 1183 EP - 92 JF - Neuropharmacology JO - Neuropharmacology VL - 61 IS - 8 N2 - Most recreational users of 3, 4-methylenedioxymethamphetamine (MDMA or "ecstasy") also take cannabis, in part because cannabis can reduce the dysphoric symptoms of the ecstasy come-down such as agitation and insomnia. Although previous animal studies have examined the acute effects of co-administering MDMA and Δ(9)-tetrahydrocannabinol (THC), which is the major psychoactive ingredient in cannabis, research on chronic exposure to this drug combination is lacking. Therefore, the present study was conducted to investigate the effects of chronic adolescent administration of both THC and MDMA on behavior and on regional serotonin transporter (SERT) binding and serotonin (5-HT) concentrations as indices of serotonergic system integrity. Male Sprague-Dawley rats were divided into four drug administration groups: (1) MDMA alone, (2) THC alone, (3) MDMA plus THC, and (4) vehicle controls. MDMA (2 × 10 mg/kg × 4 h) was administered every fifth day from postnatal day (PD) 35 to 60 to simulate intermittent recreational ecstasy use, whereas THC (5mg/kg) was given once daily over the same time period to simulate heavy cannabis use. THC unexpectedly produced a modest hyperthermic effect when administered alone, but in animals co-treated with both THC and MDMA, there was an attenuation of MDMA-induced hyperthermia on dosing days. Subsequent testing conducted after a drug washout period revealed that THC reduced MDMA-related behavioral changes in the emergence and social interaction tests of anxiety-like behavior and also blunted the MDMA-induced decrease in exploratory behavior in the hole-board test. THC additionally attenuated MDMA -induced decreases in 5-HT levels and in SERT binding in the frontal cortex, parietal cortex, and striatum, but not in the hippocampus. These results suggest that chronic co-administration of THC during adolescence can provide some protection against various adverse physiological, behavioral, and neurochemical effects produced by MDMA. SN - 1873-7064 UR - https://www.unboundmedicine.com/medline/citation/21763331/Chronic_administration_of_THC_prevents_the_behavioral_effects_of_intermittent_adolescent_MDMA_administration_and_attenuates_MDMA_induced_hyperthermia_and_neurotoxicity_in_rats_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0028-3908(11)00278-4 DB - PRIME DP - Unbound Medicine ER -