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Concentration-dependent suppression by beta-adrenergic antagonists of the shift in ocular dominance following
Abstract:
We showed that beta-adrenergic receptor antagonists blocked the shift in ocular dominance following brief monocular deprivation in young kittens. Localized microperfusion of propranolol into the kitten visual cortex reduced the expected shift in the ocular dominance approximately 2 mm away from the center of perfusion. The blocking effect, however, did not reach an area approximately 5 mm from the perfusion center, suggesting that beta blockers work in a concentration-dependent fashion in the present paradigm. We further studied the concentration-effect relationship by widely changing the concentration of beta blockers (propranolol and sotalol) stored in an osmotic minipump. The proportion of binocular cells increased from 0.13 to 0.67 when the concentration of propranolol was increased from 10(-6)M to 10(-2)M, giving the half-maximum effect (binocularity, 0.40) at about 10(-4)M propranolol. However, the maximum binocularity obtained with the sotalol perfusion under the comparable condition was apparently much lower (0.45) than that with propranolol. Accordingly, the half-maximum binocularity (0.30) was obtained at about 10(-5)M sotalol. We also noted the presence of a linear, inverse relation between the logarithmic concentration of the beta blockers and the extent of the shift in ocular dominance as measured by the proportion of monocular cells which responded exclusively to stimulation of the nondeprived eye. The latter decreased from 0.75 to 0.25, when the former was increased from 10(-6)M to 10(-2)M (in an osmotic minipump). The two beta blockers behaved similarly in this correlation. The intracortical spread of locally perfused [3H]propranolol was studied at the end of the cortical perfusion which lasted for a week. The radioactivity was highest at the perfusion center and rapidly declined with increasing distance, leveling off approximately 3 mm from the perfusion center. The average "dilution factor" of locally perfused [3H]propranolol was calculated as about 1/170 of the original solution in an area of physiological recordings (approximately 2 mm from the perfusion center). Applying the "dilution factor" of 1/170, we estimated the approximate concentration of beta blockers needed at the recording sites to obtain the half-maximum effect; it was about 5.8 X 10(-8)M for sotalol. Taken together, the present results were interpreted as suggesting that there is a positive correlation between the number of activated beta-adrenergic receptors within the visual cortex and the extent of changes in ocular dominance following monocular deprivation.(ABSTRACT TRUNCATED AT 250 WORDS)