Dopamine receptor antagonists prevent expression, but not development, of morphine sensitization

Area of Science:

• Neuroscience
• Pharmacology
• Behavioral Science

Background:

• Morphine induces locomotor-stimulating effects and can lead to sensitization, a process where repeated drug exposure enhances the response.
• Dopamine pathways in the brain are implicated in the rewarding and motor effects of drugs, including morphine.

Purpose of the Study:

• To investigate the role of dopamine D1 and D2 receptors in the development and expression of morphine-induced locomotor sensitization.
• To determine if dopamine receptor antagonists prevent the initiation or expression of sensitization to morphine's locomotor effects.

Main Methods:

• Rats were treated with morphine (10 mg/kg) daily for 12 days, with co-administration of dopamine D1 receptor antagonist SCH 23390 (0.25 mg/kg) or dopamine D2 receptor antagonist eticlopride (0.1 mg/kg).
• Locomotor activity was measured to assess sensitization.
• Electrophysiological recordings in the nucleus accumbens were performed to evaluate dopamine D1 receptor sensitivity.

Main Results:

• Both SCH 23390 and eticlopride suppressed the expression of sensitized locomotor activity when administered with morphine during the 12-day treatment.
• Despite the suppression during treatment, subsequent administration of morphine alone resulted in significant locomotor sensitization in both antagonist groups.
• Electrophysiological data did not support the development of dopamine D1 receptor supersensitivity in rats treated with SCH 23390.

Conclusions:

• Dopamine receptor stimulation appears to be involved in the expression, but not the development, of morphine-induced locomotor sensitization.
• Selective dopamine D1 and D2 receptor antagonists can inhibit the expression of sensitization during chronic morphine treatment.
• The findings suggest a complex interaction between dopamine signaling and the neuroadaptations underlying morphine sensitization.