GABAB receptors modulate synaptically-evoked responses in the rat dentate gyrus, in vivo.
We assessed the effects of systemically injected baclofen, a GABAB agonist, on single and paired-pulse responses in the dentate gyrus of urethane-anesthetized rats, in vivo. Baclofen (10 mg/kg) significantly increased the duration of single excitatory responses. This increase was blocked by the GABAB receptor antagonist, CGP 35348, indicating that baclofen was acting through GABAB receptors. To determine the mechanism underlying this increase in response duration, the NMDA antagonist, D-2-amino-5-phosphonopentanoic acid (D-APV), was administered intracerebroventricularly (i.c.v.) after baclofen. D-APV by itself had no effect on the duration of the population excitatory post-synaptic potential (EPSP). However, when infused after baclofen, D-APV blocked the baclofen induced increase in EPSP duration. This indicates the prolonged EPSP duration caused by baclofen resulted from an enhancement of an NMDA receptor mediated component of the response. We then examined the effect of baclofen on population responses to paired stimuli. Baclofen attenuated paired-pulse inhibition of population spike amplitudes at a 25 ms interstimulus interval. CGP-35348 reduced the effect of baclofen on paired-pulse inhibition, indicating that baclofen suppressed paired-pulse inhibition by acting on GABAB receptors. In contrast to its disinhibitory effect at the 25 ms interval, baclofen had an inhibitory effect on responses evoked at a 150 ms interstimulus interval. Under control conditions, we observed that when stimuli were delivered 150 ms apart, both the EPSP duration and population spike amplitude evoked by the second stimulus were enhanced. Baclofen suppressed this enhancement.(ABSTRACT TRUNCATED AT 250 WORDS)
Brucato
F H
FH
Department of Medicine, Duke University Medical Center, Durham, NC 27705, USA.
Mott
D D
DD
Lewis
D V
DV
Swartzwelder
H S
HS
D000818:Animals; D001418:Baclofen / Q000494:pharmacology; D005071:Evoked Potentials / Q000187:drug effects; D005260:Female; D058786:GABA-B Receptor Agonists; D058788:GABA-B Receptor Antagonists; D006624:Hippocampus / Q000502:physiology*; D009433:Neural Inhibition / Q000187:drug effects / Q000502:physiology; D009943:Organophosphorus Compounds / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D011963:Receptors, GABA-A / Q000187:drug effects; D018080:Receptors, GABA-B / Q000502:physiology*
D058786:GABA-B Receptor Agonists; D058788:GABA-B Receptor Antagonists; D009943:Organophosphorus Compounds; D011963:Receptors, GABA-A; D018080:Receptors, GABA-B; C066430:CGP 35348; D001418:Baclofen