Blockade of histamine H2 receptors of the periaqueductal gray and inferior colliculus induces fear-like behaviors

Electrical and chemical stimulation of the dorsal periaqueductal gray matter (dPAG) and the inferior colliculus (IC) induces escape behavior, usually accompanied by autonomic responses and antinociception. Recently, we presented evidence for a tonic inhibitory control exerted by H2 histamine receptors on defensive behaviors generated in these midbrain tectum sites. Since treatments of these areas that elicit the defensive behavior repertoire frequently also have anxiogenic effects, we here used the elevated plus-maze (EPM) test for assessing the effects of microinjections of histamine (5–40 nmol), dimaprit (5–10 nmol) and ranitidine (10–30 nmol) into either dPAG or IC, which have a relative abundance of histamine-containing cells and histaminergic receptors. Dimaprit is an agonist and ranitidine is an antagonist of H2 histamine receptors. Immediately after the injections, the animals were submitted to the EPM test. Whereas dPAG injections of dimaprit had no behavioral effects, histamine (40 nmol) caused a significant reduction in exploratory activity. On the other hand, ranitidine alone or following saline had aversive-like effects in both structures, i.e. reduced open arm, but not closed arm, entries. This pattern is usually interpreted as representing an anxiogenic effect. These effects were more pronounced after injection into dPAG than into IC. Freezing, the most prominent effect produced by ranitidine, was significantly inhibited by histamine as well as dimaprit. Thus, H2 receptor blockade has fear-like action in the midbrain tectum with predominance in the dPAG. Such an action can be understood as a concomitant of defensive behavior, which has been shown to be a consequence of H2 receptor antagonism in both dPAG and IC. The functional significance of the different effects of H2 receptor blockade in dPAG and IC is discussed in the light of the probable distinct roles of these structures in the organization of defensive behavior.