Dual actions of morphine on the central nervous system: parallel actions of beta-endorphin and ACTH.
In the studies described above, the intracerebral microinjection technique was used to study the actions of morphine at morphine-sensitive sites, the periaqueductal gray (PAG) and the midbrain reticular formation (MRF). In the PAG, morphine exerted dual actions: inhibitory and excitatory. In the MRF, morphine exerted an excitatory action only, indicating that the dual actions of morphine are dissociable and site specific. Following microinjection into the PAG, beta-endorphin exerted an inhibitory, and ACTH an excitatory, action, i.e., each duplicated one of morphine's dual actions. These results indicated that receptors for the endogenously occurring peptides, beta-endorphin and ACTH, may play a role in morphine's potent pharmacological actions. Although these studies do not shed direct light on the physiological role of these neuropeptides and their receptors, nor on their potential roles in the functional regulation of brain (especially in diseased mental states), it may be permissible to offer some speculations. We previously proposed that beta-endorphin may be an endogenous antipsychotogen, and that a deficiency in brain beta-endorphin may underlie some forms of psychopathology. In view of beta-endorphin's biosynthetic link to ACTH, and the behavioral effects of beta-endorphin (sedated immobility) that was found to be opposite in kind to those of ACTH (fearful hyperreactivity) following administration into brain, it is possible that these two neuropeptides may have regulatory roles in maintaining a functional balance in brain. (It may be speculated that these biosynthetically linked neuropeptides served survival functions of "flight" and "freeze" in our evolutionary ancestors.) An imbalance in the bioavailability of either of the two neuropeptides, e.g., a deficiency of beta-endorphin or an excess of ACTH (perhaps due to the lack of the specific enzymes that cleave these peptides from their parent prohormone) may be an etiological factor in some forms of chronic functional disorders of the brain.
D000324:Adrenocorticotropic Hormone / Q000494:pharmacology*; D000698:Analgesia; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D001921:Brain / Q000187:drug effects*; D004723:Endorphins / Q000494:pharmacology*; D007267:Injections; D008297:Male; D009020:Morphine / Q000008:administration & dosage / Q000494:pharmacology*; D009270:Naloxone / Q000494:pharmacology; D010913:Pituitary-Adrenal System / Q000502:physiology; D051381:Rats; D011919:Rats, Inbred Strains; D001615:beta-Endorphin
D004723:Endorphins; D009270:Naloxone; D001615:beta-Endorphin; D009020:Morphine; D000324:Adrenocorticotropic Hormone