Antagonistic effects of growth hormone-releasing factor (GRF) and somatostatin on locomotor activity: GRF-induced hyperkinetic syndrome.
In order to investigate the potential antagonistic actions of the two main neuroregulators of the somatotropinergic system (GRF-SS-GH-SM axis), growth hormone-releasing factor (GRF) and somatostatin (SS) at the central level, the effects of GRF and SS on locomotor activity (LA) were studied in a computerized system. Male Wistar rats (N = 6-9 per group) received i.p. or i.c.v. GRF(1-44)NH2 or SS(1-14) in doses ranging from 0.1-30 micrograms, and LA was automatically recorded in the OUCEM-86 system (Osaka University Computerized Electronic Maze) for 30-min periods. The peripheral administration of SS (1 microgram, i.p.) did not alter LA, while GRF (1 microgram, i.p.) increased LA from 20.35 +/- 4.18 to 36.25 +/- 6.98 IO/min (p less than 0.005). After central injection, SS (1 microgram; i.c.v.) decreased LA from 31.16 +/- 6.90 to 20.88 +/- 2.82 IO/min (p less than 0.005) and GRF (1 microgram, i.c.v.) increased LA to 47.60 +/- 5.35 IO/min (p less than 0.005). SS- and GRF-induced LA changes were time- and dose-dependent (SS: ED50 = 1.83 nmol, Emax = 6.10 nmol; GRF: ED50 = 99.1 pmol, Emax = 1.98 nmol). The maximum effect of GRF appeared during the first 5 min, showing activity 10-15 sec post-injection, while the lowest activity induced by SS was registered 15-30 min after injection, although a significant reduction in LA was detected 5-10 sec after i.c.v. administration. With doses higher than 10 micrograms (i.c.v.) SS provoked "barrel rotation", tremors and stereotyped behaviors. The GRF-induced hyperkinetic syndrome showed a linear pattern with doses up to 10 micrograms, and a plateau with 10-15 micrograms. Doses higher than 20 micrograms induced convulsion, uncontrolled movements and a high death rate during the following 12-24 h. In conclusion, according to the present results, GRF and SS exert antagonistic effects on LA in a time- and dose-dependent manner, the former stimulating LA, and the latter inhibiting it.
Cacabelos
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Department of Human Physiology, Faculty of Medicine, Madrid Complutense University, Spain.
Niigawa
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H
Alvarez
X A
XA
Muñoz
M D
MD
Nishimura
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T
Rubia
F J
FJ
D000818:Animals; D001289:Attention Deficit Disorder with Hyperactivity / Q000139:chemically induced*; D001522:Behavior, Animal / Q000187:drug effects; D003199:Computer Systems; D013007:Growth Hormone-Releasing Hormone / Q000008:administration & dosage / Q000494:pharmacology*; D007274:Injections, Intraperitoneal; D007275:Injections, Intravenous; D008297:Male; D009043:Motor Activity / Q000187:drug effects*; D051381:Rats; D011919:Rats, Inbred Strains; D013004:Somatostatin / Q000008:administration & dosage / Q000494:pharmacology*
D013004:Somatostatin; D013007:Growth Hormone-Releasing Hormone