Amphetamine sensitization is accompanied by an increase in prelimbic cortex activity.

Area of Science:

• Neuroscience
• Psychopharmacology
• Addiction Research

Background:

• Drug addiction is linked to medial prefrontal cortex (mPFC) dysfunction.
• The precise neuronal activity changes in the mPFC that contribute to the reinforcing effects of addictive drugs remain poorly understood.

Purpose of the Study:

• To investigate the modifications in neuronal activity within the prelimbic (PL) cortex, a region of the mPFC, during amphetamine sensitization.
• To elucidate the role of mPFC neuronal hyperexcitability in the development of amphetamine-induced behavioral changes.

Main Methods:

• Single-unit recordings were performed in anesthetized rats exhibiting locomotor sensitization to amphetamine.
• Neuronal firing rate (FR) and burst rate were analyzed in the prelimbic (PL) cortex of control and sensitized rats following acute amphetamine administration.

Main Results:

• In control rats, amphetamine primarily inhibited neuronal firing, with the response inversely related to basal FR.
• Sensitized rats displayed a greater proportion of excited neurons, and amphetamine's effect on FR was independent of basal FR.
• Acute amphetamine decreased burst rate in control rats but increased it in sensitized rats, indicating heightened neuronal excitability.

Conclusions:

• Amphetamine sensitization leads to hyperexcitability of mPFC neurons.
• Increased mPFC activity during early withdrawal may strengthen the PL-Nucleus Accumbens pathway, facilitating amphetamine-induced locomotor sensitization.