This laboratory works cooperatively with that of R.J. Blanchard,applying analyses of defensive and aggressive behaviors developed in that laboratory to an understanding of anxiety-related psychopathologies. A major component of this effort involves analysis of the effects of psychoactive drugs on particular defensive behaviors. To facilitate this analysis we have developed test batteries for both rats and mice that elicit and measure each of several defensive behaviors, and also evaluate sedation and coordination, in a single, 15-minute test. In these rat and mouse defense test batteries, drugs effective against generalized anxiety disorder selectively impact two particular defensive behaviors, risk assessment and defensive threat/attack. This pattern of results is notspecific to drug class, as it is seen with classic benzodiazepines such as diazepam and chlordiazepoxide, as well as 5-HT1A agonists such as buspirone and gepirone. In contrast, drugs that are effective against panic disorder reduce an additional defensive behavior, flight, without systematically altering risk assessment, defensive threat/attack, or, freezing.

A recent review of some 19 psychoactive drugs evaluated in the Mouse Defense Test Battery (MDTB) indicated that all of the panicolytic drugs reduced flight; all of the panicogenic drugs enhanced flight, and all of the drugs without effect on human panic disorder failed to alter flight in this test, indicating that MDTB flight behaviors provide an extremely precise prediction of drug effects on panic disorder. Again, these effects do not depend on drug class, as drugs from a number of different classes, with different mechanisms of effect, may increase, or decrease panic in people. A particularly interesting recent finding has been that cocaine, a drug that has been shown to increase panic attacks in people, enhances flight behaviors in both rats and mice, and after both intravenous and intraperitoneal administration.

An additional focus of this laboratory is on analysis of gender differences in defensive behavior. Gender is increasingly recognized as a major factor in the incidence of a wide variety of defense-related psychopathologies such as anxiety and depression, with women showing rates of these disorders that are roughly twice that of men. In line with these well-established finding, we have reported that female rats also show higher rates of particular defensive behaviors, notably risk assessment and behavioral inhibition, than do males. Both the drug effects on defensive behavior, and the gender differences in particular defensive behaviors suggest homologies between the defensive behaviors of laboratory rodents, and those of humans, with disturbances in these biobehavioral systems constituting a major mechanism for defense-related psychopathologies.

Ribeiro-Barbosa ER, Canteras NS, Cezario AF, Blanchard RJ, Blanchard DC. 2005. An alternative experimental procedure for studying predator-related defensive responses. Neurosci Biobehav Rev. 29; 1255-63.

Blanchard, DC, Canteras NS, Markham CM, Pentkowski NS and Blanchard RJ. 2005. Lesions of structures showing for expression to cat presentation: Effects on responsivity to a cat, cat odor, and nonpredator threat. Neurosci Biobehav Rev. 29: 1243-53.

Apfelbach R., Blanchard, DC, Blanchard RJ, Hayes RA , and McGregor, I. 2005. The effects of predator odors in mammalian prey species: A review of field and laboratory studies. Neurosci Biobehav Rev. 29: 1123:42

Blanchard RJ, Griebel G, Farrokhi C, Markham C, Yang M, Blanchard DC. AVP V1b selective antagonist SSR149415 blocks aggressive behaviors in hamsters. Pharmacol Biochem Behav. 2005 Jan;80(1):189-197.

Wall PM, Blanchard RJ, Yang M, Blanchard DC. Differential effects of infralimbic vs. ventromedial orbital PFC lidocaine infusions in CD-1 mice on defensive responding in the mouse defense test battery and rat exposure test. Brain Res. 2004 Sep 10;1020(1-2):73-85.

Markham CM, Blanchard DC, Canteras NS, Cuyno CD, Blanchard RJ. Modulation of predatory odor processing following lesions to the dorsal premammillary nucleus. Neurosci Lett. 2004 Nov 30;372(1-2):22-6.

Wall PM, Blanchard RJ, Markham C, Yang M, Blanchard DC. 2004. Infralimbic D1 receptor agonist effects on spontaneous novelty exploration and anxiety-like defensive responding in CD-1 mice. Behav Brain Res. 2004 Jun 4;152(1):67-79.

Blanchard, D.C., Yang M., Hebert, M.A., and Blanchard, R.J. (2006) Defensive behaviors. In Fink,G. (Ed) Encyclopedia of Stress, 2nd edition. New York, Academic Press, p. 652-656.

Blanchard, D.C., and Blanchard, R.J. 2005 Stress and Aggressive Behaviors. In Nelson, R.Biology of Aggression, Oxford University Press, Oxford, pp 275-294.

Gerlai, R, Blanchard, R, and Blanchard DC. 2006 Animal models of anxiety: The ethological perspective. In Fisch, GS and Flint J (Eds.) Contemporary Clinical Neuroscience: Transgenic and Knockout Models of Neuropsychiatric Disorders. Fisch, GS and Flint J (Eds.) Humana Press, Totowa, NJ pp 221-236.