Paradoxical Ventral Tegmental Area GABA Signaling Drives Enhanced Morphine Reward After Adolescent Nicotine.

ABSTRACT:

Background

An important yet poorly understood risk factor for opioid use disorder is adolescent nicotine use. We investigated the neural mechanisms underlying this understudied interaction.

Methods

Male and female adolescent mice received 2 weeks of nicotine water (Adol Nic) or plain water (Adol Water). In adulthood, mice underwent 3 morphine tests: conditioned place preference (CPP), locomotor sensitization, and two-bottle choice. Ex vivo ventral tegmental area (VTA) brain slices were assessed via patch clamp for GABA (gamma-aminobutyric acid) and dopamine (DA) neuron responses to morphine. Finally, VTA GABA neurons were chemogenetically inhibited during morphine CPP.

Results

In adulthood, Adol Nic mice showed greater morphine CPP, more choice-based morphine consumpt

SUBMITTER: Wittenberg RE 

PROVIDER: S-EPMC12445159 | biostudies-literature | 2026 Mar

REPOSITORIES: biostudies-literature