Effects of N-methyl-D-aspartate agonists and antagonists in rats discriminating amphetamine.
The present study assessed the interactions between N-methyl-D-aspartate (NMDA) agonists or antagonists and the discriminative stimulus effects of amphetamine. Adult male Sprague-Dawley rats were trained to discriminate 0.5 mg/kg (i.p.) of amphetamine from saline under a two-lever fixed-ratio schedule of food reinforcement. During test sessions, i.p. injections of the glycine site agonist D-cycloserine, the ion-channel blocker dizocilpine and the competitive antagonist CGP 43487 were coadministered with i.p. saline or with a full range of doses of amphetamine. D-Cycloserine did not substitute for amphetamine and attenuated the cueing effects of the drug. Both dizocilpine and CGP 43487 engendered intermediate levels of amphetamine-appropriate responses and potentiated the stimulus properties of amphetamine; however, the effects of CGP 43487 were very small and not dose-dependent. In an ancillary experiment, the training dose of amphetamine was reduced to 0.25mg/kg; under these conditions dizocilpine, but not CGP 43487, produced full substitution for the discriminative stimulus effects of amphetamine. These results show that drugs affecting NMDA receptor-based neurotransmission can modulate the discriminative stimulus effects of amphetamine.
Gaiardi
M
M
Department of Pharmacology, University of Bologna, Italy. gaia@biocfarm.unibo.it
Gubellini
C
C
Dall'Olio
R
R
Gandolfi
O
O
Bartoletti
M
M
D015763:2-Amino-5-phosphonovalerate / Q000031:analogs & derivatives* / Q000494:pharmacology; D000661:Amphetamine / Q000494:pharmacology*; D000818:Animals; D000697:Central Nervous System Stimulants / Q000494:pharmacology*; D003523:Cycloserine / Q000494:pharmacology; D004192:Discrimination, Psychological / Q000187:drug effects*; D016291:Dizocilpine Maleate / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology*; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000819:agonists* / Q000037:antagonists & inhibitors*
D000697:Central Nervous System Stimulants; D018690:Excitatory Amino Acid Agonists; D018691:Excitatory Amino Acid Antagonists; D016194:Receptors, N-Methyl-D-Aspartate; C087755:CGP 43487; D016291:Dizocilpine Maleate; D015763:2-Amino-5-phosphonovalerate; D003523:Cycloserine; D000661:Amphetamine