Cholecystokinin antagonizes morphine induced hypoactivity and hyperactivity in hamsters

Area of Science:

• Neuroscience
• Behavioral Pharmacology
• Endocrinology

Background:

• Opioid peptides play a crucial role in regulating behavior.
• Cholecystokinin (CCK) is a peptide with diverse physiological functions, including neuromodulation.
• CCK-8 is a known antagonist of opioid agonists in various behavioral contexts.

Purpose of the Study:

• To investigate the dose-dependent effects of cholecystokinin octapeptide (CCK-8) on morphine-induced activity changes in golden Syrian hamsters.
• To determine if CCK-8 can antagonize both the hypoactivity and hyperactivity elicited by morphine.
• To provide further support for the hypothesis that endogenous CCK-8 modulates endogenous opioid peptide activity.

Main Methods:

• Three experimental replications were conducted using golden Syrian hamsters.
• Animals received injections of either saline or CCK-8 (25, 50, or 75 µg/kg), followed by either saline or morphine sulfate (15 mg/kg).
• Running wheel activity was monitored for three hours post-injection in four groups: SAL/SAL, CCK/SAL, SAL/MS, and CCK/MS.

Main Results:

• A CCK-8 dose of 25 µg/kg significantly blocked morphine-induced hypoactivity 40-60 minutes after opiate administration.
• A CCK-8 dose of 75 µg/kg significantly blocked morphine-induced hyperactivity 80-100 minutes after opiate administration.
• The effects of CCK-8 were dose-dependent and time-specific in antagonizing morphine's behavioral effects.

Conclusions:

• CCK-8 exhibits a dose-dependent antagonism of morphine's effects on hamster activity.
• These findings support the role of CCK-8 as a modulator of opioid peptide systems in behavior.
• Endogenous CCK-8 may act as a physiological counterbalance to endogenous opioid peptides in behavioral control.