Behavioral sensitization to amphetamine is dependent on corticosteroid receptor activation

Area of Science:

• Neuroscience
• Pharmacology
• Endocrinology

Background:

• Behavioral sensitization, a phenomenon of increased motor activity after repeated drug administration, is crucial for understanding drug addiction.
• The role of the adrenal system and corticosteroids in modulating neuroplasticity and drug-induced behaviors remains incompletely understood.

Purpose of the Study:

• To investigate the necessity of corticosteroids for the development of behavioral sensitization to amphetamine.
• To determine which corticosteroid receptor subtypes mediate this effect.

Main Methods:

• Thirty rats were administered amphetamine injections (1.5 mg/kg) spaced six days apart, with locomotor activity monitored.
• Rats underwent either adrenalectomy or sham surgery before the second amphetamine injection.
• Corticosteroid replacement therapies (corticosterone, deoxycorticosterone, dexamethasone) were administered to assess their effects.

Main Results:

• Sham-operated rats displayed significant behavioral sensitization to amphetamine.
• Adrenalectomy abolished amphetamine-induced behavioral sensitization.
• While corticosterone and deoxycorticosterone failed to reverse this effect, dexamethasone (a glucocorticoid) fully restored and potentiated sensitization.

Conclusions:

• Corticosteroids are necessary for the development of behavioral sensitization to amphetamine in rats.
• The findings strongly suggest that corticosteroids act primarily through the type II (glucocorticoid) receptor to facilitate dopaminergic system sensitization.