Cross-sensitization between phencyclidine and (-) but not (+) pentazocine

Area of Science:

• Neuroscience
• Psychopharmacology
• Behavioral Pharmacology

Background:

• Behavioral sensitization is a well-documented phenomenon following repeated administration of psychomotor stimulants like amphetamine and cocaine, and psychotomimetics such as phencyclidine (PCP).
• The effects of repeated sigma ligand administration on locomotor activity and the potential for cross-sensitization with known psychotomimetics remain largely unexplored.
• Sigma ligands, including pentazocine, are known to interact with various neurotransmitter systems, suggesting potential roles in modulating behavior.

Purpose of the Study:

• To determine the psychomotor stimulant effects of the sigma ligand (+)pentazocine and its enantiomer, (-)pentazocine.
• To investigate whether reciprocal cross-sensitization occurs between repeated treatment with (+) or (-)pentazocine and PCP-induced locomotor activity and ambulation.

Main Methods:

• Adult female Sprague-Dawley rats were utilized for all experiments.
• Locomotor activity and ambulation were quantified using an automated photoelectric system.
• Behavioral sensitization was assessed following repeated IP injections of (+)pentazocine, (-)pentazocine, or PCP, with subsequent challenge doses to evaluate locomotor responses.

Main Results:

• Acute administration of either (+) or (-)pentazocine produced minimal, non-significant locomotor stimulant effects.
• Repeated administration of (+)pentazocine did not result in behavioral sensitization.
• However, repeated injections of (-)pentazocine or PCP led to significant behavioral sensitization.
• Rats sensitized to (-)pentazocine exhibited cross-sensitization to PCP-induced locomotion, and vice versa, indicating reciprocal cross-sensitization.

Conclusions:

• The findings suggest that the (+) and (-) enantiomers of pentazocine act at distinct receptor sites, mediating different behavioral outcomes.
• (-)Pentazocine demonstrates a profile of locomotor stimulant effects and sensitization properties more akin to PCP.
• The observed reciprocal cross-sensitization between (-)pentazocine and PCP highlights a shared neurobiological mechanism underlying their psychomotor stimulant and sensitizing effects.