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Context-dependent cocaine sensitization: differential effect of haloperidol on development versus expression
1Biological Psychiatry Branch, National Institute of Mental Health 20892.
Pharmacology, Biochemistry, and Behavior
|November 1, 1989
Summary
Cocaine sensitization in rats is context-dependent, requiring specific environmental cues for its development and expression. Preventing initial cocaine effects blocks subsequent sensitization, suggesting a conditioning mechanism.
Area of Science:
- Neuroscience
- Behavioral Pharmacology
Background:
- Psychomotor stimulants, such as cocaine, can induce behavioral sensitization with repeated administration.
- Behavioral sensitization is characterized by progressively amplified motor activity in response to stimulant exposure.
- The neurobiological underpinnings and contextual dependencies of stimulant-induced sensitization require further investigation.
Purpose of the Study:
- To investigate a novel two-day sensitization paradigm for cocaine in rats.
- To determine the role of environmental context and pharmacological interventions in the development and expression of cocaine sensitization.
- To explore the potential of this model for understanding clinical neuroleptic nonresponsiveness.
Main Methods:
- Rats received a single high dose of cocaine (40 mg/kg) or saline on day 1, followed by a challenge dose (10 mg/kg) on day 2.
- Environmental context was manipulated to assess conditioning and stimulus generalization.
- Pharmacological agents (haloperidol, diazepam) were administered to block cocaine-induced hyperactivity on day 1 or to prevent sensitization expression on day 2.
Main Results:
- Rats receiving cocaine on day 1 exhibited increased locomotor response to a challenge dose on day 2, but only if the context was similar.
- Preventing cocaine-induced hyperactivity on day 1 with haloperidol or diazepam abolished sensitization on day 2.
- Haloperidol administered on day 1 prevented sensitization development, but when given before the day 2 challenge dose, it did not prevent sensitization expression.
Conclusions:
- Cocaine sensitization in this paradigm is a conditioned, context-dependent phenomenon.
- The development of sensitization involves initial environmental conditioning, while its expression may involve separate neurobiological pathways.
- This model offers insights into clinical neuroleptic nonresponsiveness in stimulant-induced behavioral changes.