Modulation of adenylyl cyclase activity by baclofen in the developing rat brain: difference between cortex, thalamus...

Ontogenetic changes in the levels of GABA(B) receptors and their ability to modulate adenylyl cyclase (AC) activity were analyzed in rat cortex, thalamus and hippocampus. The relative numbers of GABA(B) receptors (measured as saturable, high-affinity [(3)H](-)baclofen binding sites) in cortex and thalamus were high already at postnatal day 1 (PD 1) and they reached a maximum at PD 25 and PD 12, respectively. There were no detectable high-affinity [(3)H](-)baclofen binding sites in hippocampus between birth and PD 12 and low-affinity [(3)H](-)baclofen binding attained at PD 12 did not change in adulthood (PD 90). Whereas GTP-stimulated AC activity in cortex and thalamus was depressed by baclofen, it was enhanced in hippocampus. These data indicate that the inhibitory effect of baclofen on AC in cortex and thalamus is primarily mediated through the alpha subunits of G(i)/G(o) proteins. The stimulatory effect of baclofen in hippocampus may be explained by engagement of Gbetagamma subunits.