title: Chronic administration of THC prevents the behavioral effects of intermittent adolescent MDMA administration and attenuates MDMA-induced hyperthermia and neurotoxicity in rats.
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.affiliation: Neuroscience and Behavior Program, University of Massachusetts, Amherst, MA 01003, USA. yshen@cns.umass.edu
authors.forename: Erica Y
authors.initials: EY
authors.lastname: Shen
authors.forename: Syed F
authors.initials: SF
authors.lastname: Ali
authors.forename: Jerrold S
authors.initials: JS
authors.lastname: Meyer
mesh_terms: D018759:Adrenergic Uptake Inhibitors / Q000009:adverse effects; D000367:Age Factors; D000704:Analysis of Variance; D000818:Animals; D000831:Animals, Newborn; D001522:Behavior, Animal / Q000187:drug effects*; D001831:Body Temperature / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D004195:Disease Models, Animal; D013759:Dronabinol / Q000008:administration & dosage*; D004334:Drug Administration Schedule; D005106:Exploratory Behavior / Q000187:drug effects; D005334:Fever / Q000139:chemically induced / Q000517:prevention & control*; D006897:Hydroxyindoleacetic Acid / Q000378:metabolism; D007398:Interpersonal Relations; D008297:Male; D018817:N-Methyl-3,4-methylenedioxyamphetamine / Q000009:adverse effects; D020258:Neurotoxicity Syndromes / Q000209:etiology / Q000473:pathology / Q000517:prevention & control*; D011485:Protein Binding / Q000187:drug effects; D011619:Psychotropic Drugs / Q000008:administration & dosage*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011930:Reaction Time / Q000187:drug effects; D012701:Serotonin / Q000378:metabolism
chemical_list: D018759:Adrenergic Uptake Inhibitors; D011619:Psychotropic Drugs; D012701:Serotonin; D006897:Hydroxyindoleacetic Acid; D013759:Dronabinol; D018817:N-Methyl-3,4-methylenedioxyamphetamine