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Published on: November 6, 2018
Behavioral activation induced by D(2)-like receptor stimulation during opiate withdrawal
J P Druhan1, C L Walters, G Aston-Jones
1Center for Neurobiology and Behavior, Department of Psychiatry, University of Pennsylvania Medical Center, Philadelphia 19104, USA. druhan@mail.med.upenn.edu
Summary
Opiate withdrawal surprisingly increases locomotion when D(2)-like receptors are stimulated. This finding suggests a mechanism for how withdrawal may drive drug-seeking behavior during detoxification.
Area of Science:
- Neuroscience
- Pharmacology
- Addiction Research
Background:
- Opiate withdrawal paradoxically reduces dopamine release and behavioral responding in animal models.
- This presents a challenge in understanding how withdrawal motivates drug-seeking behavior despite suppressed functioning.
Purpose of the Study:
- To investigate factors that enhance behavioral activity during opiate withdrawal.
- To explore the role of dopamine receptor subtypes in mediating withdrawal-induced behavioral changes.
Main Methods:
- Administered D(2)-like agonists (propylnorapomorphine HCl, quinpirole) and a D(1)-like agonist (SKF 38393) during opiate withdrawal in rats.
- Used eticlopride (D(2)-like antagonist) to block receptor activity.
- Induced withdrawal via morphine pellet implantation and naltrexone antagonism.
Main Results:
- D(2)-like agonists, but not D(1)-like agonists, significantly increased locomotor activity during opiate withdrawal.
- This locomotor activation was dependent on D(2)-like receptor stimulation and specific to withdrawal states.
- The effects were observed during pellet-induced withdrawal but not with acute morphine antagonism.
Conclusions:
- Opiate withdrawal potentiates the locomotor-activating effects of D(2)-like receptor stimulation.
- This heightened responsiveness may facilitate behavioral activation during opiate detoxification and contribute to drug-seeking behaviors.
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