Effects of GABAB activation and inhibition on vestibulo-ocular and optokinetic responses in the pigmented rat.
The effects of the GABAB agonist baclofen and the GABAB antagonist CGP 35348, given separately or simultaneously, on the central vestibular system of pigmented rats have been evaluated. Drugs were administered either intramuscularly or intracerebroventricularly. Eye movements were recorded during vestibular, optokinetic and combined visual-vestibular stimulation. Activation of the GABAB receptors by baclofen caused a dose related disturbance of the system, manifested by (1) a decrease of the optokinetic gain, (2) a reduced ability to suppress nystagmus during conflicting vestibular and visual input, and (3) a disability to maintain the eccentric eye position upon a spontaneous saccade. All these effects could be inhibited in a dose-dependent fashion by CGP 35348, suggesting that the findings are specifically related to the GABAB receptor. Given separately, the antagonist did not affect the mentioned parameters. During horizontal acceleratory/deceleratory stimulation in darkness baclofen caused a biphasic pattern in the dose-response curves. Small amounts of baclofen caused an increase of the gain and of the duration of poststimulatory nystagmus, while high doses had a depressive action on the same parameters. The stimulating effect of baclofen could be inhibited or even reversed by CGP 35348, which has a depressive effect per se, similar to the effects of baclofen given in the upper range of doses.
Niklasson
M
M
Department of Otolaryngology, Faculty of Health Sciences, University Hospital, Linköping, Sweden.
Tham
R
R
Larsby
B
B
Eriksson
B
B
D000818:Animals; D001418:Baclofen / Q000037:antagonists & inhibitors / Q000494:pharmacology; D003624:Darkness; D004305:Dose-Response Relationship, Drug; D058786:GABA-B Receptor Agonists; D058788:GABA-B Receptor Antagonists; D007273:Injections, Intramuscular; D007276:Injections, Intraventricular; D017120:Nystagmus, Optokinetic / Q000187:drug effects*; D009943:Organophosphorus Compounds / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D012027:Reflex, Vestibulo-Ocular / Q000187:drug effects*
D058786:GABA-B Receptor Agonists; D058788:GABA-B Receptor Antagonists; D009943:Organophosphorus Compounds; C066430:CGP 35348; D001418:Baclofen