Anxiolytic-like action in mice treated with nitrous oxide and oral triazolam or diazepam

Abstract

Few animal studies have explored the interaction of nitrous oxide (N2O) with a benzodiazepine (BNZ) administered by the oral route, as used in clinical procedures involving "conscious sedation". The purpose of this study was to evaluate the relative "anxiolytic-like" and sedative effectiveness of N2O, oral triazolam (TRIAZ; Halcion) or oral diazepam (DIAZ; Valium), either alone or in various combinations of drugs and doses. One hundred and twelve Swiss Webster male mice, 35-45 days old, were assigned to 28 groups, each of which contained four mice. The mouse staircase test was used for the assessment of anxiety (number of rearings) and sedation (number of steps ascended). Three doses of oral TRIAZ (0.1, 0.3, 1.0 mg/kg) or DIAZ (2.0, 3.5, 5.0 mg/kg) were given in combination with room air, or N2O/O2 at a N2O concentration of 25, 50 or 75%. Each mouse was tested once. N2O alone did not reduce NR in any concentration, but caused a significant increase in locomotion. DIAZ without N2O reduced NR only with the middle and high doses, but the addition of N2O significantly enhanced the anxiolytic-like effect of all DIAZ doses. TRIAZ, alone, reduced NR only in the highest dose, but added N2O resulted in anxiolytic-like behavior with all three TRIAZ doses. The sedative effects of the BNZs were extremely variable. Only the middle dose of DIAZ plus 25% N2O unequivocally reduced the number of steps ascended, i.e., caused sedation. TRIAZ lacked the inverted U-shaped dose-response relationship with NR usually seen with DIAZ. TRIAZ, therefore, provides better dose control. This behavioral animal model indicates that the optimal combinations for reduction of anxiety-like behavior with minimal effects on sedation are 0.1 mg/kg oral TRIAZ with 25% N2O or 2.0 mg/kg oral DIAZ with 25% N2O.

Diazepam effects on Ehrlich tumor growth and macrophage activity in mice

“…Indeed, diazepam induced no effects on ascitic volume and number of tumor cells after 0.3 or 1.0 mg/kg, for 7 days. This finding might be relevant since the usual anxyolitic doses of diazepam range from 1.0 to 2.0 mg/ kg/day in rats and mice (Chen et al, 2004;Gries et al, 2005). Thus, it seems plausible to suggest that the effects of diazepam on tumor growth are not related to the anxiolytic effects of this compound, which is known to be related to an action on GABA-A receptor-associated sites within the CNS.…”

“…The vehicle of diazepam, as provided by the manufacturer per our request, was diluted 20% in Ringer solution, being used as control solution (0.1 ml/10 g). Diazepam is frequently employed as an anxiolytic or sedative drug in mice at a dose varying from 1 to 2 mg/kg (Chen et al, 2004;Gries et al, 2005). Experiments previously performed in our lab showed that diazepam (1.0 to 3.0 mg/kg) decreased peritoneal macrophage activity in mice (Massoco and Palermo-Neto, 1999) and impaired host defense against M. bovis in hamsters (Righi et al, 1999).…”

Voluntary Oral Ingestion of a Sedative Prior to Euthanasia with CO2: Behavioural Responses of Mice

“…During the sedation period, we found a reduction of rearing and lid walking, and an increase of the duration of ataxia, immobility and recumbency, with higher tiletaminezolazepam dosage. Rearing has been used as a measure of exploration and anxiety in mice [31][32][33]; thus, a decrease in the frequency of rearing could be interpreted as a sign of reduced exploratory and anxiety-like behaviour; however, these latter studies recorded…”

In Vivo Psychopharmacological Investigation of Delphinium Denudatum and Amaranthus Spinosus Extracts on Wistar Rats

“…These effects of both drugs could be due to the interaction of flavonoids, alkaloids, tannins, triterpenoids, and steroids (chemical constituents of the plants) with the GABA/benzodiazepine receptor complex in the brain ( Kumar, 2000 ); however, flavonoids generally possessed the anxiolytic activity ( Herrera et al, 2008 ; Mahendra & Bisht, 2011 ), hence both drugs contain flavonoids biochemical. Further studies are required to explain the exact mechanism of action of DDE and ASE (200 and 400 mg/kg) and their combination, also to isolate the main chemical constituents responsible for these types of activities.…”