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Reduced behavioral effectiveness of ACTH(1-24) after a second administration: interaction with opiates.
J Jolles1, V M Wiegant, W H Gispen
1Division of Molecular Neurobiology, Rudolf Magnus Institute for Pharmacology, State University of Utrecht, Padualaan 8, Utrecht, The Netherlands.
Neuroscience Letters
|July 17, 2009
Summary
Repeated intraventricular administration of adrenocorticotropic hormone (ACTH) reduces ACTH-induced grooming. This effect is opiate-mediated, as naloxone pretreatment blocks the reduction in grooming behavior.
Area of Science:
- Neuroendocrinology
- Behavioral Neuroscience
Background:
- Adrenocorticotropic hormone (ACTH) plays a role in stress response and behavior.
- Opiates and ACTH can modulate behavioral responses.
Purpose of the Study:
- To investigate the effects of repeated intraventricular ACTH administration on ACTH-induced grooming.
- To determine the mechanisms underlying the observed behavioral changes.
Main Methods:
- Repeated intraventricular administration of ACTH in a rodent model.
- Assessment of grooming behavior following ACTH challenge.
- Pretreatment with beta-endorphin, (D-Phe(7))ACTH(4-10), morphine, and the opiate antagonist naloxone.
Main Results:
- Repeated ACTH administration significantly reduced subsequent ACTH-induced grooming.
- Pre-injection with beta-endorphin, (D-Phe(7))ACTH(4-10), or morphine also attenuated the grooming response.
- The reduction in grooming was not due to corticosteroid feedback.
- Naloxone pretreatment blocked the ACTH-induced reduction in grooming.
Conclusions:
- Repeated intraventricular ACTH administration induces tolerance to its own behavioral effects.
- The observed tolerance is mediated by the endogenous opiate system.
- This suggests a complex interaction between the ACTH and opiate systems in regulating behavior.
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