Abstract
Behavioral sensitization of mice (male STD-ddy) to d-methamphetamine (MAP) and its correlation with the neurochemical alterations in cerebral catecholaminergic systems were investigated following the repeated administration of MAP (5 mg/kg, i.p. x 2/day, 5 days). MAP-pretreated mice showed an enhancement in MAP-stimulated locomotor activity following the readministration of MAP (0.625 mg/kg). The metabolic turnovers of cerebral norepinephrine (NE) and dopamine (DA) showed a significant decrease in these sensitized mice. The activities of tyrosine hydroxylase. DOPA decarboxylase, monoamine oxidase and catechol-O-methyltransferase, however, showed no change under the same experimental conditions. On the other hand, the repeated MAP pretreatment induced the enhancement of the specific bindings of [(3)H]dihydroalprenolol and [(3)H]spiperone to cerebral synaptic membrane, which resulted from the increase of B(max) values. Furthermore, pretreatments of mice with propranolol (10 mg/kg) and haloperidol (0.1 mg/kg) inhibited the development of behavioral sensitization to MAP. These results suggest that the supersensitivity in cerebral ?-adrenergic and dopaminergic receptors may be involved in behavioral sensitization to MAP.
Published Version
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