Referenced in: none

Automatically associated channels: Kv2.1

Title: Chronic administration of NMDA glycine partial agonists induces tolerance in the Porsolt swim test.

Authors: T Lopes, P Neubauer, K M Boje

Journal, date & volume: Pharmacol. Biochem. Behav., 1997 Dec , 58, 1059-64

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/9408214

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.