Escape behavior under tonic inhibitory control of histamine H(2)-receptor mediated mechanisms in the midbrain tectum.
The dorsal periaqueductal gray matter (DPAG), superior and inferior colliculus have been implicated in the control of defense reactions in the midbrain. Electrical and chemical stimulation of these structures induces escape behavior, usually accompanied by autonomic responses and antinociception. GABA, 5-HT, opioids, excitatory amino acids and neuropeptides have been postulated to participate in the organization of such defensive reactions in the midbrain tectum. However, little attention has been given to a possible involvement of histamine in the generation of such behavior. To examine this issue in the present study, we assessed the effects of injections into the midbrain tectum of histamine and the H(1) and H(2) receptor antagonists, chlorpheniramine and ranitidine on the behavioral manifestations of the defense reaction. The effects of these drugs were also examined on antinociception, which has been considered to be an inherent component of the defense reaction. Thus, the animals were submitted to an open field test and after 30 min, antinociceptive behavior was measured with the aid of the tail-flick test. The results show that histamine reduced exploratory activity without causing motor deficit, as evaluated by the rotarod test. Ranitidine led to a dose-dependent behavioral activation, with clear signs of fear, whereas no apparent effect was observed following injections of chlorpheniramine. Antinociception always followed the escape reaction induced by the H(2) receptor blocker ranitidine. The present results suggest that H(2) receptors may be involved in the control of escape behavior and antinociception following activation of the neural substrates of fear in the midbrain tectum.