Recombinant human growth hormone affects the density and functionality of GABAB receptors in the male rat brain.
The beneficial effects of growth hormone (GH) on memory and learning have previously been confirmed in both humans and in animal models. An important role of GABAB receptors for multiple forms of learning and memory has also been reported. In this study, we examined the effect of GH on the density and functionality of the metabotropic GABAB receptors in the rat brain. Male Sprague-Dawley rats (n = 24) divided into 3 groups were injected twice daily with recombinant human GH (0.07 or 0.7 IU/kg) for 7 days. The effects of the hormone were determined by quantitative autoradiography and by GABAB stimulated [(35)S]-GTPγS binding using the selective GABAB receptor agonist baclofen. The results demonstrate moderate but significant alterations in both receptor density and functionality in a number of brain regions. For example, a dose-dependent upregulation of GABAB receptors was found in the cingulate cortex, primary motor cortex and caudate putamen, whereas attenuation in the receptor density was encountered in, for example, the medial geniculate nucleus. Although the GH-induced effects on the GABAB receptor in brain areas associated with cognition were fairly pronounced, they were significant and we propose that the physiological responses observed after GH administration at least partly can be mediated through a mechanism involving GABAB receptors.
Division of Biological Research on Drug Dependence, Department of Pharmaceutical Biosciences, Uppsala University, Uppsala, Sweden.
Alfhild
A
Grönbladh
Jenny
J
Johansson
Fred
F
Nyberg
Mathias
M
Hallberg
D000818:Animals; D001418:Baclofen / Q000494:pharmacology; D001921:Brain / Q000187:drug effects* / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D016244:Guanosine 5'-O-(3-Thiotriphosphate) / Q000378:metabolism; D019382:Human Growth Hormone / Q000494:pharmacology*; D008297:Male; D051381:Rats; D018080:Receptors, GABA-B / Q000378:metabolism*; D011994:Recombinant Proteins / Q000494:pharmacology; D013462:Sulfur Radioisotopes
D018080:Receptors, GABA-B; D011994:Recombinant Proteins; D013462:Sulfur Radioisotopes; D019382:Human Growth Hormone; D016244:Guanosine 5'-O-(3-Thiotriphosphate); D001418:Baclofen