Thalamo-accumbal circuit adaptations following extended oxycodone abstinence

Area of Science:

• Neuroscience
• Addiction Research
• Behavioral Pharmacology

Background:

• Opioid use disorder (OUD) involves compulsive drug seeking and relapse.
• Incubation of craving increases relapse risk after abstinence.
• Sex differences in OUD relapse vulnerability are not fully understood.

Purpose of the Study:

• To investigate sex differences in oxycodone relapse and craving.
• To examine the impact of abstinence duration on neurotransmission in the PVT-NAcSh pathway.
• To correlate circuit-level plasticity with sex-specific relapse vulnerability.

Main Methods:

• Oxycodone self-administration and forced abstinence in male and female rats.
• Optogenetics and ex vivo electrophysiology to assess synaptic function in the PVT-NAcSh pathway.
• Measurement of synaptic strength, glutamate release probability, and MSN excitability after acute and prolonged abstinence.

Main Results:

• No sex differences in oxycodone intake or withdrawal symptoms.
• Females exhibited higher cue-induced relapse after prolonged (14 days) but not acute (1 day) abstinence.
• Prolonged abstinence similarly increased PVT-NAcSh synaptic strength and glutamate release probability in both sexes.

Conclusions:

• Shared neuroadaptations in the PVT-NAcSh pathway occur with oxycodone abstinence in both sexes.
• Heightened relapse vulnerability in females after prolonged abstinence is not explained by PVT-NAcSh plasticity alone.
• Additional neural circuits likely mediate sex-specific relapse mechanisms in opioid use disorder.