Neurotransmitter uptake in various brain regions of chronically morphinized rats

Rats were long-term morphine-intoxicated by a fluid-diet model ensuring an equal nutrient intake in morphinized and control rats. Uptake of neurotransmitters and D-ala2-met5-enkephalinamide (Enk) was studied in the particulate fractions (obtained at 10,000 g) from well defined brain regions of long-term intoxicated and morphine withdrawn rats. In control animals the accumulation of [3H]glutamate and [3H]gamma-aminobutyric acid (GABA) reached the highest tissue/medium (T/M) ratio values, 30-120, in the regions studied while monoamine T/M values were 2-10. No active uptake of [3H]Enk could be demonstrated. Striatum showed the most evident modifications in neurotransmitter uptake. In this region the equilibrium T/M ratio for [3H]glutamate and [3H]GABA was significantly lower in intoxicated rats versus controls. Moreover, the T/M ratio for [3H]5-hydroxytryptamine (5-HT) was lower, while that for [3H]dopamine (DA) was higher in abstinent rats in comparison with the controls. [3H]glutamate and [3H]GABA uptakes were also significantly lower, respectively, in frontal cortex, hippocampus and brain stem in intoxicated rats, while [3H]5-HT uptake was significantly lower in hypothalamus after morphine withdrawal. The possible involvement of the endogenous opioid system in the etiology of the alterations is discussed.