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Minimized tolerance to the suppressive effects of CCK8 on operant responding
Abstract:
This study was designed to determine if tolerance to cholecystokinin octapeptide (CCK8) could be prevented or minimized by spacing injections, and if an appetitive operant conditioning paradigm provides a sensitive baseline to test the effects of CCK8. Male Sprague-Dawley rats were trained to press a lever for water according to a fixed-interval 60-sec schedule of reinforcement. After response rate stabilized, rats were given a series of CCK8 (0.04 mg/kg, ip) injections spaced several days apart. The first injection of CCK8 produced complete response suppression during the 30-min test session, while later injections produced partial or complete suppression. Thus, tolerance to CCK8, as measured by operant response rate, may be minimized if injections are appropriately spaced.
Insights
Spacing cholecystokinin octapeptide (CCK8) injections can minimize tolerance development. This finding suggests that careful timing of CCK8 administration may preserve its effects in behavioral studies.
Area of Science:
- Neuroscience
- Behavioral Pharmacology
Background:
- Cholecystokinin octapeptide (CCK8) is a gastrointestinal hormone with known effects on satiety and feeding behavior.
- Repeated administration of CCK8 can lead to the development of tolerance, diminishing its physiological effects.
- Understanding tolerance mechanisms is crucial for accurately interpreting CCK8's role in behavior.
Purpose of the Study:
- To investigate if spaced injections of CCK8 can prevent or reduce tolerance.
- To evaluate the utility of an appetitive operant conditioning paradigm for assessing CCK8 effects.
Main Methods:
- Male Sprague-Dawley rats were trained to press a lever for water under a fixed-interval 60-sec schedule.
- After response stabilization, rats received spaced injections of CCK8 (0.04 mg/kg, ip).
- Operant response rates were monitored to assess CCK8's effect on behavior.
Main Results:
- The initial CCK8 injection caused complete suppression of lever pressing.
- Subsequent, spaced injections resulted in partial or complete suppression, indicating reduced tolerance.
- The operant conditioning paradigm effectively detected changes in CCK8's behavioral effects.
Conclusions:
- Tolerance to CCK8, assessed via operant response rate, can be minimized by spacing injections.
- Appetitive operant conditioning serves as a sensitive method for studying CCK8 effects and tolerance.
- Optimizing injection schedules may be key to maintaining CCK8 efficacy in research.