Bovine growth hormone transgenic mice display alterations in locomotor activity and brain monoamine neurochemistry

Recent clinical and experimental data indicate a role for GH in mechanisms related to anhedonia/hedonia, psychic energy, and reward. In the present st udy we have investigated whether bovine GH (bGH) transgenic mice and nontra nsgenic controls differ in spontaneous locomotor activity, a behavioral res ponse related to brain dopamine (DA) and reward mechanisms, as well as in l ocomotor activity response to drugs of abuse known to interfere with brain DA systems. The animals were tested far locomotor activity once a week for 4 weeks. When first exposed to the test apparatus, bGH transgenic animals d isplayed significantly more locomotor activity than controls during the ent ire registration period (1 h). One week later, after acute pretreatment wit h saline, the two groups did not differ in locomotor activity, whereas at t he third test occasion, bGH mice were significantly more stimulated by d-am phetamine (1 mg/kg, ip) than controls. At the fourth test, a tendency for a larger locomotor stimulatory effect of ethanol (2.5 g/kg, ip) was observed in bGH transgenic mice. bGH mice displayed increased tissue levels of sero tonin and 6-hydroxyindoleacetic acid in several brain regions, decreased Db levels in the brain stem, and decreased levels of the DA metabolite 3,4-di hydroxyphenylacetic acid in the mesencephalon and diencephalon, compared wi th controls. In conclusion, bGH mice display more spontaneous locomotor act ivity than nontransgenic controls in a novel environment and possibly also a disturbed habituation process. The finding that bGH mice were also more s ensitive to d-amphetamine-induced locomotor activity may suggest that the b ehavioral differences observed are related to differences in brain DA syste ms, indicating a hyperresponsiveness of these systems in bGH transgenic mic e. These findings may constitute a neurochemical basis for the reported psy chic effects of GH in humans.