An experimental evaluation of dependence liability of methaqualone diphenhydramine (combination) and methaqualone in rats

Abstract

In the present study the drugs (Methaqualone + diphenhydramine or Methaqualone alone) were administered daily in a liquid diet to different groups of rats for 3 weeks. Each week the doses of the drugs were increased and daily records of body weight, mean rectal temperature and spontaneous motor activity (SPM) were maintained. During the first week, tolerance to both the drugs was observed when the animals received 152.4 mg/kg^-1/day of methaqualone (MQ) and 140.0+14.0 mg/kg^-1/day of methaqualone + diphenhydramine (MQ+D) respectively. In the second week the doses were further increased to 302.0 mg/kg^-1/day of MQ and 277.8+27.7 mg/kg^-1/day of MQ+D respectively.

At the end of the second week complete tolerance developed to increased doses of MQ but not to the MQ+D combination. In the third week the doses were further increased to 406.6 mg/kg^-1/day of methaqualone and 383.4+38.3 mg/kg^-1/day of MQ+D respectively. At the end of this week although there was partial recovery but, compared to the controls, a significant lowering (P<0.05) of mean rectal temperature and spontaneous motor activity persisted in both groups thus showing an incomplete tolerance to larger doses of both MQ and the MQ+D combination. When the drugs were withdrawn after the third week, both MQ as well as MQ+D treated groups of rats exhibited an increased susceptibility to audiogenic stimuli of, but MQ+D treated animals showed an even greater susceptibility to such stimuli and also a fall in body weight. Further, 50% of rats in MQ+D group died during convulsions while there were no deaths in the group treated with MQ alone. The results of this study suggest that the MQ+D combination causes a more severe degree of physical dependence than MQ alone.