pharmacology Biochemistry & Behavior, Vol.37, pp. 633-638.©PergamonPress plc,1990. Printedin theU.S.^. 0091-3057/90 $3.00 + .00 Methylenedioxymethamphetamine' s Capacity to Establish Place Preferences and Modify Intake of an Alcoholic Beverage EDWARD J. BILSKY, YIZHAO HUI, CHRISTOPHER L. HUBBELL AND LARRY D. REID 1 Department of Psychology, Rensselaer Polytechnic Institute, Troy, NY 12180-3590 Received 27 February 1990 BILSKY, E. J., Y. HUI, C. L. HUBBELL AND L. D. REID. Methylenediox3,methamphetamine's capacityto establishplace pref- erences andmodifyintakeof an alcoholic beverage.PHARMACOLBIOCHEM BEHAV 37(4) 633-638, 1990.--Doses of 0.2, 2.0, 6.3 and 20.0 mg/kg 3,4-methylenedioxymethamphetamine(MDMA), a putative neurotoxin at serotonergic neurons and a recre- ational drug, were assessed using Sprague-Dawley rats in the conditioned place preference (CPP) test. Also, the drug's effects on intake of a sweetened ethanol solution (ES) was assessed. The CPP testing involved multiple administrations of MDMA with fre- quent periodic testing (weekly for 4 weeks) of MDMA's effects. Doses of 2.0 and 6.3 mg/kg produced positive CPPs with every test. MDMA also affected rats' gain in body weight across the 4 weeks of dosing. The 2.0 mg/kg dose reliably incremented gain in body Weight,while the 20.0 rog/kg dose reliablyattenuated it. In the drinking experiment, water-deprivedrats (22 h/day)were given daily opportunities to drink either tap water or a sweetened ES. When stable intakes were achieved, MDMA's effects were assessed across repeated daily administrations (12 days) and subsequently (16 days). MDMA, dose-relatedly, decreased intake of both ES and water with the highest dose leading to marked loss in body weight. Intakes of fluids were not modified markedly subsequent to dosing. In summary, MDMA is an agent that produces a positive CPP (providing further evidence for MDMA's abuse liability), produces changes in weight gain and nonselectively reduces fluid intake among fluid-deprived rats. MDMA Methylenedioxymethamphetamine Positive affect Conditioned place preference Ethanol intake Drugs of abuse FROM a number of perspectives, 3,4-methylenedioxymeth- brain-stimulation reward among rats, an index of the potential amphetamine (MDMA), commonly referred to as "ecstasy," euphoric properties of a drug. It does so, however, across a rather is an interesting drug. People have reported that MDMA pro- restricted range of doses (approximately I to 4 mg/kg) (10). This duces pleasant feelings (1) and, consequently, it has become a may be due to MDMA's debilitating effects that could be pm- drug of abuse. This is mirrored by the finding that MDMA is duced by larger does. The procedures of CPP testing assess an self-administered by laboratory subjects (12). There is also evi- agent's effects, after conditioning, while the rats are undrugged. dence leading to the conclusion that MDMA is toxic to serotoner- Therefore, CPP testing is useful for assessing the affective states gic neurons [for a review, see (17)]. A loss of central serotonergic produced by doses of drugs which produce debilitating effects activity could lead to increases in intake of alcoholic beverages, (2). Consequently, in this experiment, we tested the effects of a since perturbations of serotonergic systems have been shown to range of doses of MDMA using the CPP test. affect rats' intakes of alcoholic beverages (6, 8, 16, 20, 23). With It has been reported that MDMA is toxic to serotonergic sys- these ideas as background, the effects of MDMA were examined tems even after only a single subcutaneous (SC) administration of under two circumstances: (a) as an agent in a test for conditioned 20 mg/kg (15). Given such toxicity, it is possible that MDMA's place preferences (CPPs) and (b) as an agent that might modify effects might change rapidly across repeated administrations. The intake of a sweetened alcoholic beverage. CPP test allows for repeated conditioning and testing of an agent's effects, and thus an assessment can be made of an agent's ability EXPERIMENT I to sustain a CPP. Continued conditioning with morphine, for ex- MDMA has been previously shown to lower the threshold for ample, sustains or even enhances a CPP (14). Consequently, the _Requests for reprints should be addressed to L. D. Reid. 633