DISCRIMINATIVE STIMULUS EFFECTS OF MAGNESIUM-CHLORIDE - SUBSTITUTION STUDIES WITH MONOAMINE UPTAKE INHIBITORS AND N-METHYL-D-ASPARTATE ANTAGONISTS

Previous studies suggest that magnesium chloride may have discriminati ve stimulus effects that partially overlap with those of noncompetitiv e N-methyl-D-aspartate antagonists as well as certain monoamine uptake inhibitors. In our study, rats were trained to discriminate 100 mg/kg magnesium chloride from saline and its discriminative stimulus effect s were characterized with respect to N-methyl-D-aspartate receptor and manoamine transporter functions in substitution tests, The discrimina tive stimulus effects of magnesium chloride were acquired within a mod erate number of training sessions and showed dose-related substitution after either subcutaneous (3-300 mg/kg) or intracerebroventricular (0 .3-300 mu g) administration, The intracerebroventricular administratio n of magnesium chloride was over 4000 times more potent than its s.c. administration. The monoamine uptake inhibitors cocaine, GBR 12909, ta lsupram and citalopram fully substituted (greater than or equal to 90% magnesium-appropriate responses) for magnesium chloride in the majori ty of subjects tested and the group averages reached a maximum of 72 t o 82% responses on the magnesium-appropriate lever. Based on relative potency analysis, the rank order of potency of these four drugs for pr oducing magnesium-appropriate responses was talsupram = cocaine > cita lopram = GBR 12909, The N-methyl-D-aspartate receptor antagonists dizo cilpine, phencyclidine and NPC 17742 engendered maximum group averages of 49 to 65% responses on the magnesium-appropriate lever. The result s suggest that the centrally mediated discriminative stimulus effects of magnesium chloride may be more directly related to interactions wit h monoamine neurotransmitter functions than to N-methyl-D-aspartate re ceptor blockade.