Chronic exposure (8 weeks) to sequential application of mild stressors caused the increase in the density (Bmax) of beta-adrenergic and 5-HT2 receptors in the rat cerebral cortex. MK-801 given chronically (5 weeks) decreased beta-adrenergic receptors density in both control and stressed rats, whereas it decreased the density of 5-HT2 receptors in control rats only. On the other hand, imipramine administered for 5 weeks reduced the number of beta-adrenergic and 5-HT2 receptors in both control and stressed rats.

Animals↗

PubMedDate not supplied

Rewarding properties of non-competitive and competitive NMDA antagonists as measured by place preference conditioning in rats.

The conditioned place preference paradigm was used to evaluate rewarding properties of non-competitive (MK-801) and competitive (CGP 37849) antagonists of NMDA receptors. Both MK-801 (0.3 mg/kg ip) and CGP 37849 (5, 10, 20 mg/kg ip), administered in association with the initially non-preferred (white) side of the two-arms chamber, caused a significant increase in the time spent on that side in a post-conditioning test. These results show that both non-competitive and competitive antagonists of NMDA receptors are rewarding in animals and may therefore have an abuse potential in humans.

2-Amino-5-phosphonovalerate↗

PubMedDate not supplied

New evidence for the antidepressant activity of MK-801, a non-competitive antagonist of NMDA receptors.

Chronic treatment with MK-801 (0.3 mg/kg ip; 5 weeks) reverses the deficit in rewarded behavior (anhedonia) measured as a decrease in the consumption of a palatable sucrose solution in a chronic mild stress model of depression in rats. The magnitude of this effect was comparable to that observed following similar administration of imipramine (10 mg/kg ip; 5 weeks), used as a standard antidepressant drug.

Animals↗

PubMedDate not supplied

Effect of chronic mild stress and prolonged treatment with imipramine on the levels of endogenous Met-enkephalin in the rat dopaminergic mesolimbic system.

Chronic mild stress (CMS)-an established behavioral model of anhedonia, which is one of the core symptoms of major depression-significantly decreases the level of endogenous Met-enkephalin in the rat nucleus accumbens (NAS). Prolonged administration of imipramine (IMI)-the most often used antidepressant drug-increases the level of this peptide in the NAS and reverses the effect of CMS, when administered simultaneously to the animals subjected to CMS. Prolonged administration of IMI decreases the level of Met-enkephalin in the ventral tegmental area (VTA) both in control rats as well as in rats subjected to CMS. Since the endogenous enkephalins have been demonstrated to influence the activity of dopaminergic projection from the VTA to the NAS, the obtained results are discussed in the light of the data pointing to the involvement of mesolimbic dopamine system both in the CMS-induced anhedonia and in the mechanism of therapeutic effect of IMI.

Animals↗

PubMedDate not supplied

Effect of chronic treatment with imipramine on interleukin 1 and interleukin 2 production by splenocytes obtained from rats subjected to a chronic mild stress model of depression.

A depression-like state was induced by chronic (3-week) exposure of Wistar rats to a very mild, unpredictable stress which is a model of depression, developed by Willner's group. Five-week daily administration of imipramine reversed the stress-induced deficit in sucrose consumption. Eight-week stress induced an increase in the ability of splenocytes to produce interleukin 1 (IL-1) and interleukin 2 (IL-2) and to proliferate after stimulation with concanavalin A. Antidepressant effects of imipramine were accompanied by a decrease in the ability of splenocytes to produce IL-1 and IL-2 and to proliferate. Administration of imipramine alone did not modify the activity of those cells.

Animals↗

PubMedDate not supplied

Humoral regulation of pancreatic blood flow.

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Animals↗