Co-administration of subeffective anxiolytic doses of diazepam and hydroxyzine in elevated zero-maze in mice.

OBJECTIVE: Benzodiazepines are from the most common drugs which are used for treatment of anxiety disorders. There are other drugs with antianxiety properties including antihistamines such as hydroxyzine, too. Body of evidence show that co-administration of two drugs which act through different mechanisms, makes the dose of each drug to be reduced, while preserving the desired effect with less adverse drug reactions. The aim of this study was to see whether co-administration of subeffective antianxiety doses of diazepam and hydroxyzine has any antianxiety effect in elevated zero-maze (EZM) in mice. METHODS: To find the highest subeffective dose of each drug, different doses of hydroxyzine from 1.5 to 24 mg/kg and diazepam in doses of 0.25, 0.5 and 1 mg/kg were injected to male mice. Thirty minutes later, the animals were placed on EZM and various parameters of anxiety were recorded by a camera to assess later. After determination of subeffective antianxiety dose of the drugs, co-administration of hydroxyzine and diazepam was done and the anxiety parameters were measured. RESULTS: In co-administration of 0.25 mg/kg of diazepam and 12 mg/kg hydroxyzine, as subeffective antianxiety doses of either drug, there were not any significant differences in main anxiety parameters, i.e., time spent in open areas and open area entries compared to control group. Hence, no anxiolytic effect was seen. CONCLUSION: It seems that subeffective doses of diazepam and hydroxyzine may not have any facilitating or synergistic effect on each other in antianxiety responses in mice.

Nitric oxide involvement in consolidation, but not retrieval phase of cognitive performance enhanced by atorvastatin in mice.

UNLABELLED: Atorvastatin, a widely-used medication in treatment of hypercholesterolemia, has shown some benefits in treating cognition impairment in Alzheimer's disease. In this study, effects of atorvastatin on spatial recognition memory and the involvement of nitric oxide (NO) has been determined on consolidation and retrieval of memory in a two-trial recognition Y-maze test. Memory was impaired using scopolamine (1mg/kg, i.p.); atorvastatin (1, 5mg/kg, p.o.) was administered, either in presence or in absence of a non-specific NO synthase inhibitor, L-NAME (3, 10mg/kg, i.p.); a specific inducible NO synthase inhibitor, aminoguanidine (100mg/kg, i.p.); and a NO precursor, L-arginine (750 mg/kg, i.p.). RESULTS: 1) atorvastatin (5mg/kg) significantly improved memory performance in a dose-dependent manner on consolidation and retrieval stage of memory in scopolamine-treated mice; 2) the beneficial effects of atorvastatin on memory consolidation was significantly reversed by L-NAME (10mg/kg) and aminoguanidine; 3) L-arginine slightly potentiated the effects of sub-effective dose of atorvastatin (1mg/kg) on memory consolidation; 4) either L-NAME (up to 10mg/kg), or aminoguanidine did not affect the memory improvement by atorvastatin on retrieval stage; 5) the effects of sub-effective dose of atorvastatin (1mg/kg) on retrieval of memory were not potentiated by L-arginine. The present study demonstrates that atorvastatin improves both consolidation and retrieval phases of memory. This effect is affected by NO synthase inhibitors and NO precursor, L-arginine, only in memory consolidation phase, but not in retrieval phase. It is concluded that NO might be involved in consolidation of spatial memory improvement by atorvastatin.

Atorvastatin improved scopolamine-induced impairment in memory acquisition in mice: involvement of nitric oxide.

UNLABELLED: Atorvastatin, an inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase, widely used in treatment of hypercholesterolemia, slows the progression of mild-to-moderate Alzheimer's disease. In this study, effects of atorvastatin on acquisition of spatial recognition memory and the involvement of nitric oxide (NO) have been determined in a two-trial recognition Y-maze test and passive avoidance. Atorvastatin (1, 5mg/kg, p.o.) was administered prior to acquisition phase, either in presence or in absence of a non-specific NO synthase inhibitor, L-NAME (3, 10mg/kg, i.p.); a specific inducible NO synthase inhibitor, aminoguanidine (100mg/kg); and a NO precursor, l-arginine (750mg/kg). RESULTS: Atorvastatin significantly improved memory performance in a dose-dependent manner in acquisition of recognition memory, in both Y-maze and passive avoidance tests. 1) Atorvastatin (5mg/kg) significantly increased both exploration time and number of arm entries in scopolamine-treated mice in Y-maze. 2) The beneficial effects of atorvastatin on memory acquisition were significantly reversed by L-NAME (3mg/kg) and aminoguanidine (100mg/kg). 3) The effects of sub-effective dose of atorvastatin (1mg/kg) on memory acquisition were not potentiated by l-arginine (750mg/kg); 4) Administration of atorvastatin (5mg/kg) significantly increased step-through latency in scopolamine-induced memory-impaired mice. 5) Beneficial effect of atorvastatin on passive avoidance was not reversed by L-NAME (up to 10mg/kg). 6) The effects of sub-effective dose of atorvastatin (1mg/kg) on passive avoidance were not potentiated by l-arginine (750mg/kg). The present study demonstrates that atorvastatin improved both short-spatial recognition memory and fear memory. As this effect is reversed by L-NAME and aminoguanidine in short-term memory acquisition, it is concluded that NO might be involved in spatial memory improvement by atorvastatin.

Suppression of nitric oxide synthesis by L-NAME reverses the beneficial effects of pioglitazone on scopolamine-induced memory impairment in mice.

UNLABELLED: Pioglitazone, an agonist of peroxisome proliferator-activated receptor gamma (PPARγ), which is widely used in treatment of type 2 diabetes, has shown some therapeutic effect in Alzheimer's disease. In this study, effects of acute pioglitazone on acquisition, consolidation and retrieval of memory, and also the involvement of nitric oxide (NO) in the effects of pioglitazone on spatial recognition memory has been investigated in a two-trial recognition Y-maze test and passive avoidance in mice. Memory impairment was induced by scopolamine (1mg/kg, i.p.). Pioglitazone (10 and 20mg/kg, p.o.) was administrated prior to either acquisition, consolidation or retention trials, while L-NAME (N-nitro-l-arginine methyl ester), a non-specific NO synthase inhibitor, was administered (10mg/kg, i.p.) 30min before each trial. RESULTS: 1) pioglitazone improved the acquisition of recognition spatial memory-impaired by scopolamine; L-NAME dramatically reversed improving effects of pioglitazone on memory acquisition; 2) pioglitazone did not change the consolidation of spatial memory, impaired by scopolamine; 3) pioglitazone improved the retrieval of spatial memory and L-NAME did not alter the beneficial effect of pioglitazone; 4) pioglitazone did not affect scopolamine-induced cognitive impairments in the passive avoidance test. The present study demonstrates the beneficial effect of acute pioglitazone administration on acquisition and retrieval of scopolamine-induced cognitive deficits. This effect was reversed only in acquisition phase by nitric oxide synthase inhibitor, L-NAME, therefore, it could be concluded that NO might be involved in the pioglitazone beneficial effect of spatial memory acquisition.

Synthesis and dopaminergic activity of some E-3-(piperidin-1-yl)-1-(4-substituted phenyl)prop-2-en-1-one derivatives.

A convenient route for the synthesis of some 2-propen-1-one derivatives with E isomeric configuration is described. The activity of the synthesized compounds was evaluated through behavioral studies of apomorphine-induced licking in animal models. It was demonstrated that most of the synthesized compounds showed moderate activity in inhibition of lickings, among which 6a, was the most active compound at 30 mg/kg.