Cocaine andd-amphetamine induce changes in central ß-adrenoceptor sensitivity: Effects of acute and chronic drug treatment

The effects of acute and chronic treatment with psychomotor stimulants on specific binding of ³H]dihydroalprenolol to ß-adrenoceptors in rat brain were examined. At a dose of 10 mg/kg both acute and chronic treatment with cocaine and chronic treatment withd-amphetamine (10 mg/kg) caused increased binding of ³H]dihydroalprenolol. The molecular mechanism for this enhanced binding appears to be augmentation of the density of ß-adrenoceptors in rat brain. At a lower dose (5 mg/kg), however, chronic administration ofd-ampethamine caused a decrease in the density of ß-adrenoceptors in rat brain. Chronic treatment with eitherd-amphetamine (10 mg/kg) or cocaine induced a marked increase in the magnitude of cyclic AMP accumulation in rat brain slices elicited by norepinephrine. Acute as well as chronic administration ofd-amphetamine in vivo inhibited the temperature-dependent uptake of ³H]norepinephrine in rat brain synaptosomal homogenates, but no such inhibition was observed after chronic or acute treatment with cocaine. The results suggest that psychomotor stimulants induced ß-adrenoceptor supersensitivity which may be involved in the phenomenon of reverse tolerance and possibly psychosis in humans. The development of ß-adrenoceptor supersensitivity does not appear to be mediated through alterations in norepinephrine transport at the presynaptic sites.