Microinjection of propranolol into the dorsal periaqueductal gray causes an anxiolytic effect in the elevated plus-maze antagonized by ritanserin

Abstract

The 5-HT1A/1B receptor antagonist propranolol was injected into the dorsal periaqueductal gray (DPAG) of rats exposed to the elevated plus-maze in order to investigate the participation in anxiety of 5-HT mechanisms operating in this brain region. Microinjection of D,L- or L-propranolol into the DPAG increased the percentage of total arm entries without affecting the total number of entries into either open or enclosed arms of the maze, an effect characteristic of anxiolytic drugs injected systemically. The doses of 5 nmol L-propranolol and 10 nmol D,L-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 L-isomer is likely to be the main one responsible for the pharmacological activity observed. In addition, the anxiolytic effect of 10 nmol D,L-propranolol was antagonized by 10 nmol of the 5-HT2/1C receptor antagonist ritanserin, previously injected into the DPAG. The present as well as previously reported results suggest that the anxiolytic effect of propranolol injected into the DPAG is due to increased release of 5-HT acting on post-synaptic 5-HT2 receptors, resultant from blockade of 5-HT1B autoreceptors that inhibit amine release from serotonergic nerve endings.