org-2766 and Disease-Models--Animal

Treatment with adrenocorticotrophic hormone (ACTH), as well as with ACTH fragments and analogues, can influence behaviour of animals and humans. Furthermore it facilitates recovery of damaged peripheral nervous tissue. The question whether ACTH/MSH peptides affect recovery processes after injury to the central nervous system as well is addressed in the present review. The effects of administration of the ACTH(4-9) analog ORG 2766 after brain lesions has been studied frequently. However, the interpretation of the available data is confused by the variability of the results. Several factors can be identified which influence the efficacy of the peptide: (i) not all behavioural tests are equally suitable to reveal a peptide effect on behavioural recovery; (ii) the affected brain area; (iii) whether cell bodies or terminals are affected; (iv) the post-operative housing conditions; and (v) the onset and duration of peptide administration. Two possible explanations of peptide efficacy on functional recovery are considered: first, the peptide may accelerate spontaneously occurring recovery processes and second, the peptide may induce compensatory mechanisms underlying functional recovery without recuperation of the damaged neurons. These compensatory mechanisms seem to rely mainly on enhanced non-selective attention by activation of limbic structures. It is as yet unknown to which receptor system ORG 2766 binds; the analog lacks affinity for the known melanocortin (MC) receptors in brain, yet ORG 2766 is able to modulate the activity of endogenous opioids and the NMDA-receptor. A modulating influence of the peptide on NMDA-receptor activity might indirectly account for both enhanced attention--with ensuing behavioural recovery--and the acceleration of spontaneous recovery.

Topics: Adrenocorticotropic Hormone; Animals; Anticonvulsants; Brain Injuries; Disease Models, Animal; Peptide Fragments

Topics: Adrenocorticotropic Hormone; Animals; Anticonvulsants; Cells, Cultured; Diabetic Neuropathies; Disease Models, Animal; Humans; Melanocyte-Stimulating Hormones; Nerve Regeneration; Nervous System Diseases; Neurons; Peptide Fragments; Pro-Opiomelanocortin; RNA, Messenger

A major side effect of cisplatin treatment is peripheral neuropathy. In the past few years we have provided evidence that the ACTH4-9 analogue ORG 2766 provides protection against this neuropathy in rats and man. In this study we investigated the development of a cisplatin-induced neuropathy and the protective and therapeutic actions of ORG 2766 in mature rats. We also studied the effects of the peptide and of growth impairment caused by food restriction on nerve conduction velocities in healthy young adult rats (not subjected to any other treatment). In the neuropathy experiment, cisplatin induced a significant decrease in sensory nerve conduction velocity (SNCV), which could be prevented by concomitant administration of ORG 2766. The SNCV of the neuropathic animals recovered to control values within 10 weeks of discontinuation of cisplatin treatment. ORG 2766 did not enhance the rate of recovery. In the young adult rats neither ORG 2766 administration nor restricted weight gain significantly influenced either the motor or the sensory nerve conduction velocity. These results validate the animal model of cisplatin-induced neuropathy.

Topics: Adrenocorticotropic Hormone; Analysis of Variance; Animals; Body Weight; Cisplatin; Disease Models, Animal; Electrophysiology; Food Deprivation; Humans; Nervous System Diseases; Neural Conduction; Neurons, Afferent; Peptide Fragments; Rats; Rats, Wistar

A procedure for placing a crush lesion in the sciatic and tibial nerve of the rat based on anatomical landmarks is described. These crush lesions are used to study the process of regeneration of peripheral nervous tissue and the beneficial effects of melanocortins on speed and quality of nerve regeneration. A new precise and rapid method for testing the return of sensory function by a locally applied electric stimulus is discussed.

Topics: Adrenocorticotropic Hormone; Animals; Disease Models, Animal; Electric Stimulation; Female; Hypesthesia; Nerve Regeneration; Peptide Fragments; Rats; Rats, Inbred Strains; Sciatic Nerve; Tibial Nerve

Short-term isolation increased the frequency of social interactions in rats tested in pairs, while pairs of rats placed in an unfamiliar test cage and subjected to a high level of illumination spent less time in active social contact. These changes in social behavior elicited by environmental manipulations were counteracted by treatment with the adrenocorticotropic hormone (4-9) analog ORG 2766. The peptide's normalizing effect may be mediated by endogenous opioid systems.

Topics: Adrenocorticotropic Hormone; Animals; Disease Models, Animal; Endorphins; Humans; Naltrexone; Peptide Fragments; Rats; Social Behavior; Social Behavior Disorders