Conditioned inhibition of amphetamine sensitization

Area of Science:

• Neuroscience
• Psychopharmacology
• Behavioral Science

Background:

• Repeated psychostimulant exposure, like amphetamine, causes sensitization, an enhanced drug response.
• Sensitization can be context-specific, regulated by cues associated with drug or no-drug experiences (conditioned inhibitors).

Purpose of the Study:

• To investigate if disrupting conditioned inhibition enables amphetamine sensitization in novel contexts.
• To identify brain regions involved in the contextual control of sensitization.

Main Methods:

• Male Sprague Dawley rats underwent a two-context amphetamine conditioning procedure.
• Conditioned inhibition was extinguished in one environment, and sensitization was tested in a separate context.
• Microinjections of baclofen/muscimol (GABA-receptor agonists) were used to inhibit the medial prefrontal cortex, basolateral amygdala, or ventral subiculum.

Main Results:

• Extinguishing drug experience led to the loss of conditioned inhibition, enabling amphetamine-induced sensitized locomotion in a drug-naive context.
• Enhanced dopamine and glutamate neurotransmission in the nucleus accumbens were observed in the new context.
• Inhibition of the medial prefrontal cortex, basolateral amygdala, or ventral subiculum blocked conditioned inhibitors from preventing sensitized locomotion.

Conclusions:

• Conditioned inhibitors play a crucial role in regulating addiction-like behaviors by controlling the context-specific expression of sensitization.
• Dopaminergic and glutamatergic brain circuitry are vital for this contextual control.