Acute and chronic effects of dextropropoxyphene on behaviour and central inhibitory neurotransmission in the rat

There was no overt evidence of the development of physical dependence, as shown by a decrease in the body weight of rats following the abrupt withdrawal of dextropropoxyphene after two weeks administration. The ambulation and rearing scores in the 'open field' apparatus were increased after chronic, but not acute drug administration and returned to control values two days following drug withdrawal. GABA turnover, determined from the rise in GABA concentrations following GABA-transaminase inhibition, was reduced in the frontal and amygdaloid cortex after acute and chronic drug administration; a compensatory rise in GABA turnover in the amygdaloid cortex occurred two days after drug withdrawal. Na+, K+, ATP'ase activity, determined in a synaptosomal fraction from the mid-brain and hippocampus, was decreased in the latter region only during drug administration; a compensatory increase in the activity of this enzyme was found two days after drug withdrawal. These results support the view that chronically administered dextropropoxyphene may cause changes in inhibitory transmission and central neurotransmitter transport.