Understanding and Preventing Violence, Volume 2: Biobehavioral Influences (1994)
Chapter: Gamma-Aminobutyric Acid - Benzodiazepine Receptors
During the past decade, remarkable advances in serotonin receptor pharmacology have promised to yield important new therapeutic options. Evidence from animal studies suggest that drugs with specific actions at certain serotonin receptors selectively decrease several types of aggressive behavior. A new class of antianxiety drugs that target certain serotonin receptors is currently finding acceptance in clinical practice. However, specific antiaggressive effects have not been demonstrated for the serotonin anxiolytics. In humans, brain imaging of serotonin receptors begins to point to distinct alterations in serotonin receptor populations in subgroups of affectively disordered patients. These ongoing developments promise to be significant for diagnostic and therapeutic applications to violent individuals.
Sensational incidents of violence have been linked to the use of hallucinogens that act at distinct serotonin receptor subtypes. However, little is known as to whether or not the action at serotonin receptors is the actual mechanism by which these substances engender violent outbursts in rare, possibly psychopathic individuals.
Gamma-Aminobutyric Acid—Benzodiazepine Receptors
Thirty percent of all synapses in the brain use gamma-aminobutyric acid (GABA), and many of the GABA-containing neurons are inhibitory in nature. This cellular inhibitory role has been postulated to apply also to the physiologic and behavioral levels, including aggression. However, the present neurochemical evidence from animal studies finds inhibitory as well as excitatory influences of GABA manipulations on different aggressive patterns in discrete brain regions.
Interest in GABA is currently intense because one subtype of GABA receptor (GABA-A) forms a supramolecular complex that also localizes benzodiazepine receptors and that also is the site of action for certain alcohol effects. These receptors are the site of action for the most important antianxiety substances that have also been used for their antiaggressive properties. Evidence from animal and human studies documents the effectiveness of benzodiazepine anxiolytic for their calming and quieting effects. However, under certain pharmacologic and physiologic conditions, at low doses benzodiazepine anxiolytics may increase aggressive behavior in animals and humans, leading sometimes to violent outbursts that are termed "paradoxical rage."
The study of the benzodiazepine-GABA-A receptor complex in
