Desipramine or glutamate antagonists synergized the antidepressant-like actions of intra-nucleus accumbens infusions of minocycline in male Wistar rats.

Minocycline produces antidepressant-like actions in male rats tested in the forced swimming test (FST) and synergizes with several glutamate receptor antagonists. However, the limbic regions implicated in the antidepressant-like actions of minocycline are unknown. The objective of the present study was to test the potential antidepressant activity of nucleus accumbens infusions of minocycline alone or combined with antidepressant drugs or with several glutamate receptor antagonists, using the time-sampling method in the FST. The results show that intra-NAcc infusions of minocycline reduced immobility (1.0 microg, P<0.05; 1.5 microg, P<0.05) by increasing climbing (1.0 microg, P<0.05; 1.5 microg, P<0.05) in the FST. Likewise, systemic injections of desipramine (P<0.05), fluoxetine (P<0.05) or several glutamate receptor antagonists: EMQMCM (P<0.05), MTEP (P<0.05) or dizocilpine (P<0.05) combined with intra-nucleus accumbens infusions of vehicle produced antidepressant-like actions. The subthreshold dose of intra-nucleus accumbens infusions of minocycline combined with systemic injections of subthreshold doses of desipramine (P<0.05) or EMQMCM (P<0.05) or MTEP (P<0.05) or dizocilpine (P<0.05) produced antidepressant-like actions. It is concluded that intra-NAcc infusions of minocycline alone or combined with systemic injections of desipramine or with systemic injections of several glutamate receptor antagonists produced antidepressant-like actions in the FST.

Antidepressant-like actions of minocycline combined with several glutamate antagonists.

This study tested the potential antidepressant activity of minocycline alone or combined with two traditional antidepressant drugs or several glutamate receptor antagonists, using the time sampling method in the forced swimming test. Results showed that: desipramine (10.0 mg/kg, P<0.05; 15.0 mg/kg, P<0.05), minocycline (60.0 mg/kg, P<0.05; 80.0 mg/kg, P<0.05) and EMQMCM (1.5 mg/kg, P<0.05; 2.0 mg/kg, P<0.05), reduced immobility by increasing climbing. Fluoxetine (20.0 mg/kg, P<0.05; 25.0 mg/kg, P<0.05) reduced immobility by increasing swimming. MTEP (5.0 mg/kg, P<0.05; 10.0 mg/kg, P<0.05) and dizolcipine (1.0 mg/kg, P<0.05; 1.5 mg/kg, P<0.05) reduced immobility by increasing swimming and climbing. Combination experiments showed that a subthreshold dose of minocycline (50.0 mg/kg) synergized the antidepressant-like actions of subthreshold doses of: desipramine (5.0 mg/kg; P<0.05), EMQMCM (0.6 mg/kg; P<0.05), MTEP (2.5 mg/kg; P<0.05) and dizolcipine (0.5 mg/kg; P<0.05). In conclusion, minocycline produced antidepressant-like actions in the FST and subthreshold dose of minocycline combined with subthreshold dose of desipramine and several glutamate receptor antagonists and produced antidepressant-like actions.

Antidepressant-like and anxiolytic-like actions of the mGlu5 receptor antagonist MTEP, microinjected into lateral septal nuclei of male Wistar rats.

This study describes the effects of intra-lateral septal infusions of different doses of the mGluR5 antagonist MTEP in the DRL-72 s paradigm and the elevated plus-maze test in rats, two behavioral models known to be sensitive to antidepressant-like and anxiolytic-like drug effects, respectively. Intra-lateral septal infusions of MTEP induced a dose-dependent (5.0 microg/microl, P<0.05; 10.0 microg/microl, P<0.05) increase in reinforced lever presses and a cohesive rightward shift of the inter-response time distribution (5.0 microg/microl, P<0.05; 10.0 microg/microl, P<0.05). These effects are indicative of antidepressant-like actions of the compound. Desipramine, a prototypical antidepressant drug, induced (5.0 microg/microl; P<0.05) similar effects. In the elevated plus-maze test, intra-lateral septal infusions of MTEP (5.0 microg/microl, P<0.05; 10.0 microg/microl, P<0.05) increased the exploration of the open arms without affecting locomotion. This anxiolytic-like effect was similar to that observed with the infusion of the benzodiazepine midazolam (10.0 microg/microl; P<0.05) in the same brain area. It is concluded that intra-lateral septal infusions of the mGlu5 receptor antagonist MTEP produced antidepressant-like actions or anxiolytic-like effects in male rats.

Female Wistar rats tested during late proestrus or during pregnancy and ovariectomized rats tested after receiving progesterone or allopregnanolone displayed reduced conflict behavior.

In a conflict test based on the rat's choice between an immediate punished reinforcer or a delayed nonpunished reinforcer, anxiolytic drugs increase the number of immediate punished reinforcers. In this study, two hypotheses were tested: first, during late proestrus or during midpregnancy, female rats will display an elevated amount of immediate punished reinforcers; second, ovariectomized rats will display an elevated amount of immediate punished reinforcers when they receive anxiolytic doses of neurosteroids. Thus, female rats (n = 15) were tested repeatedly during late proestrus, diestrus, and pregnancy in the aforementioned conflict task. They displayed an elevated amount of immediate punished reinforcers during late proestrus (P < .05) and during the 14th (P < .05) and 17th (P < .05) days of pregnancy compared to diestrus or 3rd, 7th, or 20th days of pregnancy. Likewise, ovariectomized rats (n = 90) displayed an elevated amount of immediate punished reinforcers compared to control rats only when they received anxiolytic doses of progesterone (1.0-2.0 mg/kg, P < .05) or allopregnanolone (1.0-2.0 mg/kg, P < .05). In conclusion, female rats displayed reduced conflict behavior during late proestrus and pregnancy, or after received anxiolytic doses of neurosteroids.