Psychopharmacology 67, 311 - 312 (~ 980)
9 by Springer-Verlag 1980
MDA and DOM: Substituted Amphetamines thatdo not Produce Amphetamine-Like Discriminative Stimuli in the Rat
Harlan E. ShannonNational Institute on Drug Abuse, Division of Research, Addiction Research Center, Lexington, KY 40583, U.S.A.
3,4-Methylenedioxyamphetamine (MDA)and 2,5-dimethoxy-4-methylamphetamine (DOM) areamphetamine congeners that produce bothamphetamine-like and LSD-like effects. To evaluatewhether MDA and DOM should be classed withamphetamine, their capacity to produce amphetamine-like discriminative stimuli was assessed. Rats weretrained to discriminate between saline and 1.0mg/kgd-amphetamine in a two choice, discrete trial shockavoidance paradigm. Neither MDA nor DOM pro-duced any amphetamine-appropriate responding whentested over a 30-fold dose range. The specificity of theprocedure to detect amphetamine-like effects wasdemonstrated by the failure of LSD to produce anyamphetamine-appropriate responding. These resultssuggest that neither MDA nor DOM should be classedas amphetamine-like agents.
d-Amphetamine - MDA - DOM - LSD
Discriminative stimuli3,4-Methylenedioxyamphetamine (MDA) and 2,5-dimethoxy-4-methylamphetamine (DOM) are substi-tuted amphetamines which produce bothamphetamine-like and LSD-like effects (Martin et al.,1978). This mixed spectrum of effects makes pharmaco-logic classification difficult. Such classification is im-portant in assessing abuse liability as well as indetermining whether MDA and DOM haveamphetamine-like or LSDqike modes of action or bothor if they represent a unique class of drugs. Evaluationof the discriminative stimulus properties of drugs is auseful means of classification within other drug classes(Barry, 1974 for review). Therefore, to determine if
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H. E. ShannonMDA and DOM should be classed with their parentchemical compound, amphetamine, experiments wereconducted to determine whether they produceamphetamine-like discriminative stimuli in the rat.
Materials and Methods
The subjects were male CFE rats (Charles River BreedingLaboratories, Wilmington, Massachusetts) weighing 275-300 g atthe start of discrimination training. The rats were housed in a largecolony room where they had continuous access to food and water.The lights in the colony room were turned off 6 p.m-6 a.m.
A two-iever rat chamber (model 111 I-L, Grason-StadlerCo., Bolton, Massachusetts) was modified by suspending from theceiling a 25 cm long omnidirectional lever midway along the wallopposite the original levers (the choice response levers) and 2.5 cmfrom the wall. Other details of the experimental chamber andenvironmental enclosure were described previously (Shannon andHoltzman, 1976). Schedule contingencieswere controlled by a SCAT3002 system (BKP Scientific, Berlin, Massachusetts).
The procedure for training rats to discriminate between d-amphetamine and saline was similar to that described in detailelsewhere (Shannon and Holtzman, 1976). Briefly, rats were trainedin a two choice, discrete trial shock avoidance task that required theanimals to respond first on the omnidirectional lever and then on theappropriate choice response ever to terminate each trial and avoid orescape from a 1.0 mA electric shock delivered to their
d-Amphetamine (1.0 mg/kg) or saline was injected SC 30 rainbefore the start of training sessions, which were conducted 5 days aweek. Each session ended after 21 trials or 30 min, whichever camefirst. The amphetamine and saline sessions were given in doublealternation and then in random alternation until responding was atleast 95 ~ correct for four consecutive sessions (two were amphe-tamine and two were saline sessions). When a rat met this criterion,the next amphetamine and saline sessions were conducted as testsessions where a response on either choice ever terminated a trial. Ananimal was said to have acquired the discrimination if at least 18 of 20trials (exclusive of the first trial) were to the appropriate choice leverduring both test sessions. Once an animal met the acquisition criteria,training sessions, with only once choice lever being 'correct', wereconducted at least 3 days a week with amphetamine and salinesessions given in double alternation across training sessions. Testsessions, with both choice levers being 'correct'. were conducted onTuesday and Friday if responding was at least 90 % correct on
training sessionssince the previous test day. All drugs and saline were0033-3/58/80/0067/0311/$01.00