Stereoselectivity of the anxiolytic effect of propranolol microinjected into the dorsal midbrain central gray

In a previous study we have shown that microinjection of d,I-propranolol into the dorsal midbrain central gray of the rat causes an anxiolytic effect in the elevated plus-maze model which is lilkely to be mediated by endogenous 5-hydroxytryptamine. In the present experiment, the effects of 1- and d,1-propranolol were compared under the same experimental conditions. Both the I-isomer and the racemic mixture increased the percentage of open arm entries without affecting the total number of entries into either open or enclosed arms of the maze, thus reproducing the selective anxiolytic effect previously described. The doses of 5 nmol 1-propanolol and 10 nmol d,1-propranolol caused anxiolytic effects of comparable magnitude, while the doses of 2,5 nmol of the former and 5 nmol of the latter were ineffective. Therefore, the 1-isomer was nearly twice as potent as the racemic mixture, thus being responsible for the pharmacological activity observed. These results are compatible with the proposal that propranol blocks stereospecific autoreceptors in serotonergic nerve endings that inhibit neurotransmitter release

Serotonergic mediation of the anxiolytic effect of intracerebrally injected propranolol measured in the elevated plus-made

the effect of intracerebrally injected propranolol was measured in the elevated plus-maze, an animal model of anxiety. Microinjection of 10 nmol of propranolol into the dorsal midbrain central gray of the perventage of open arm entries, without affecting the total number of arm entries.This selective anxiolytic effect of propranolol was antagonized by 10 nmol of ritanserin, also injected into the dorsal midbrain. The same dose of ritanserin, given alone, did not affect the percentage of open arn entries, thought it tended to decrease the total number of entries, an indication of unspecific behavioral depression. Since propranolol is a sterospecific antagonist of presynaptic serotpnin (5-HT) antoreceptors and ritanserin is a selective blocker of type 2 5-HT recptors, the present results suggest that the anxiolytic action of propranolol in the midbrain central gray is due to release of endogenous 5-HT acting upon 5-HT2 receptors