title: Chronic administration of NMDA glycine partial agonists induces tolerance in the Porsolt swim test.
abstract: The Porsolt swim test (PST) was used to assess behavioral effects following acute or chronic treatment with two N-methyl-D-aspartate (NMDA) glycine partial agonists, 1-aminocyclopropanecarboxylic acid (ACPC), and D-cycloserine (DCS). Consistent with previous findings in mice, single intravenous doses of ACPC in rats produced a significant, dose-dependent reduction in immobility in the PST compared to saline. Single dose DCS also elicited significant dose-dependent reductions in PST immobility times. Single-dose ACPC or DCS (200 mg/kg) reduced immobility (p < 0.05) by 26 or 30%, respectively, compared to saline. However, multiple dosing with either ACPC or DCS (6 daily doses, 200 mg/kg) produced an apparent behavioral adaptation, as the immobility data were indistinguishable from chronic saline administration. Moreover, pretreatment with a 5-day course of ACPC or DCS promoted the development of a behavioral cross-tolerance following a sixth dose of DCS or ACPC, respectively. The development of a behavioral tolerance in the PST following chronic therapy of these drugs appears to be a general feature of glycine partial agonists. In toto, these findings support the hypothesis that chronic administration of NMDA glycine partial agonists produces a behavioral tolerance putatively through an adaptation of the NMDA receptor complex.
authors.affiliation: Department of Pharmaceutics, School of Pharmacy, State University of New York at Buffalo, 14260-1200, USA.
authors.forename: T
authors.initials: T
authors.lastname: Lopes
authors.forename: P
authors.initials: P
authors.lastname: Neubauer
authors.forename: K M
authors.initials: KM
authors.lastname: Boje
mesh_terms: D000818:Animals; D000929:Antidepressive Agents, Tricyclic / Q000494:pharmacology; D000963:Antimetabolites / Q000494:pharmacology; D003523:Cycloserine / Q000494:pharmacology; D003863:Depression / Q000523:psychology*; D004305:Dose-Response Relationship, Drug; D018684:Glycine Agents / Q000494:pharmacology*; D007099:Imipramine / Q000494:pharmacology; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000819:agonists*; D013315:Stress, Psychological / Q000523:psychology*; D013550:Swimming
chemical_list: D000929:Antidepressive Agents, Tricyclic; D000963:Antimetabolites; D018684:Glycine Agents; D016194:Receptors, N-Methyl-D-Aspartate; D003523:Cycloserine; D007099:Imipramine