Pharmacological Research, Vol. 40, No. 4, 1999 Article No. phrs.1999.0524, available online at http:www.idealibrary.com on ACAMPROSATE DOES NOT ANTAGONISE THE DISCRIMINATIVE STIMULUS PROPERTIES OF AMPHETAMINE AND MORPHINE IN RATS TIZIANA PASCUCCI a , IRENE CIOLI a , FRANCESCA PISETZKY a , SILVESTRO ` b b a, DUPRE , ALESSANDRA SPIRITO and PAOLO NENCINI a Institute of Medical Pharmacology, Uni ersity of Rome ‘L a Sapienza’, P.le A. Moro 5 00185, Rome, Italy and b Department of Biochemical Sciences ‘A. Rossi Fanelli’, Uni ersity of Rome ‘La Sapienza’, Rome and Centro di Biologia Molecolare, CNR, Rome Accepted 19 April 1999 Ž . Acamprosate calcium acetylhomotaurinate is a GABA derivative that prevents drinking relapses in a significant number of alcoholics. Since little is known about the interaction of Ž . acamprosate with other addictive drugs, we studied the effects of this agent as sodium salt Ž 1 . in two groups of rats trained to discriminate, respectively, morphine 1.7 mg kg i.p. or Ž 1 . amphetamine 0.5 mg kg i.p. from solvent in a two-lever fixed ratio 30 operant behaviour reinforced by water access. Accordingly to the finding that acamprosate inhibits the action Ž . of excitatory aminoacids, its effects were compared with those of dizocilpine MK-801 , an Ž 1 . NMDA antagonist. Results show that acamprosate 170 and 320 mg kg i.p. produced a slight, and not significant, shift to the left of generalization curves of both morphine and amphetamine without affecting response rates. In contrast, MK-801 potentiated response rate effects of both morphine and amphetamine without affecting their generalization curves. As far as discriminative stimuli participate in the relapsing process of addiction, our results do not predict a role of acamprosate in the prevention of amphetamine or morphine abuse relapsing. 1999 Academic Press KEY WORDS: acamprosate, morphine, D-amphetamine, drug-discrimination, rat. INTRODUCTION Ž . Acamprosate calcium acetylhomotaurinate , a syn- thetic compound structurally similar to -aminobu- Ž . tyric acid GABA , has been called an ‘anticraving drug’ for its capability of reducing relapse rates in abstinent alcoholics 1 . This property seems to be confirmed by the experimental finding that acam- prosate decreases voluntary ethanol intake in rats maintained in different conditions of access to ethanol 2, 3 . Furthermore, acamprosate has been recently found to reduce the extra amount of al- cohol consumed by rats after a period of alcohol deprivation in a dose-dependent way, without alter- ing total fluid intake or food consumption 4 . The importance of this finding is stressed by the thought that the alcohol deprivation effect could be an ani- mal model of the relapse to alcohol use 5 . How- ever, acamprosate does not seem to antagonize Corresponding author. ethanol cue nor to substitute for it in a drug-dis- crimination paradigm in the rat 6 . At the molecular level acamprosate prevents neurochemical alter- ations associated with ethanol abstinence. In partic- ular, it inhibits the enhancement of L-glutamate release in the nucleus accumbens 7, and the syn- thesis of c-fos in the hippocampus and cerebellum 8 both evoked by ethanol withdrawal. Recent find- ings show that acamprosate directly inhibits post- synaptic potentials elicited by excitatory aminoacids in the neocortex and the hippocampus 9 . This notion contrasts the initial hypothesis that acam- prosate action is mediated by GABA-A mechanisms Ž . for a review, see Littleton 10 . Drug craving has been defined as ‘the desire to Ž. experience the effect s of a previously experienced psychoactive substance’ 11 . Therefore, by defini- tion, the relapse of drug taking behaviour sustained by craving is a highly specific process. In contrast, the pharmacological block of drug craving does not appear so specific. Naltrexone, for instance, has been found to be effective in preventing the relapse of 104366189910033306$30.000 1999 Academic Press