|Vol. 7, No. 3, 2001 Page 4&5|
Poor impulse control underlies many forms of aberrant behavior, including unprovoked aggression, drug abuse, firesetting, and violent suicide. New research by Lynn Fairbanks and colleagues adds to evidence that abnormal activity of the neurotransmitter serotonin contributes to such impulsivity.
The researchers conducted two experiments involving vervet monkeys. In the first, male monkeys (divided into groups of three or four) underwent an "intruder challenge," in which researchers placed an unknown monkey in a cage at the edge of their enclosure. Later, Fairbanks et al. measured the levels of the serotonin metabolite 5-HIAA, and the dopamine metabolite HVA, in the cerebrospinal fluid (CSF) of the monkeys. Serotonin is believed to be associated with behavioral inhibition, and dopamine with behavioral activation.
The researchers report that "males that immediately rushed over and challenged the intruder were lowest in cerebrospinal fluid 5-HIAA , while those that avoided the intruder for the duration of the test had the highest concentrations." Monkeys with lower 5-HIAA levels also were more aggressive, but their aggression appeared to be a result of their impulsiveness. Analysis revealed that anxiety was not a factor in the monkeys' behavior, and that dopamine metabolite levels were not significantly linked to impulsiveness when the researchers controlled for the effects of serotonin.
In a second experiment, the researchers treated 6 monkeys with fluoxetine, a drug that increases serotonin activity, and compared their behavior to that of 12 untreated monkeys. They report that animals given fluoxetine responded less impulsively to an intruder.
Interestingly, the researchers say, the most successful monkeys were those with moderate levels of impulsivity. They note that while the impulsive, low-5-HIAA monkeys "inappropriately put themselves at high risk through a disinhibited pattern of approach to a potentially dangerous stranger," the more inhibited high-5-HIAA monkeys' conservative reaction "may be less risky than that exhibited by the impulsive animals but... could lead to reduced success in male-male competition and loss of opportunities in challenging situations." They conclude, "Variation in impulsivity-inhibition, and associated serotonin metabolism, could conceivably carry costs at the high as well as the low extreme."
While Fairbanks' primate re-search offers insights into serotonin's role in impulsive behavior, recent research by Rudolf Cardinal et al. links defects in a specific brain area—the nucleus accumbens, located at the base of the forebrain—to abnormal impulsivity.
Cardinal et al. compared rats with lesions in the nucleus accumbens core (AcbC) to nontreated rats and rats with lesions in other brain areas, training the rats to choose between two levers. One lever delivered a small food pellet immediately, while the other delivered a bigger pellet after a variable delay.
The control rats made logical choices, opting for large pellets when the delays were short but selecting smaller pellets when there were long delays in obtaining a larger pellet. The AcbC- damaged rats, however, always chose the immediate reward of the small pellet, unless the researchers eliminated the delay for receiving the larger pellet. "We have shown that damage or dysfunction of the nucleus accumbens can cause, without a doubt, impulsive choice," Cardinal and colleagues say. In addition, their study showed that damage to two related areas—the anterior cingulate cortex and the medial prefrontal cortex—had no effect on the rats' impulsive decision- making.
The researchers say their findings suggest that abnormalities of the nucleus accumbens may underlie attention deficit hyperactivity disorder. "AcbC-lesioned animals exhibited at least two signs of ADHD," they say, "locomotor hyperactivity and impulsive choice."
They conclude, "Our results provide direct evidence that the nucleus accumbens is involved in the pathogenesis of impulsive choice."
"Social impulsivity inversely associated with CSF 5-HIAA and fluoxetine exposure in vervet monkeys," Lynn A. Fairbanks, William P. Melega, Matthew J. Jorgensen, Jay R. Kaplan, and Michael T. McGuire, Neuropsychopharmacology, Vol. 24, No. 4, 2001, pp. 370-378. Address: Lynn A. Fairbanks, University of California at Los Angeles, Neuropsychiatric Institute, 760 Westwood Plaza, Los Angeles, CA 90024.
"Impulsive choice induced in rats by lesions of the nucleus accumbens core," R. N. Cardinal, D. R. Pennicott, C. L. Sugathapala, T. W. Robbins, and B. J. Everitt, Science, Vol. 292, No. 5526, June 29, 2001, pp. 2499-2501 Address: Rudolf Cardinal, Dept. of Experimental Psychology, University of Cambridge, Downing Street, Cambridge CB2 3EB, UK.
"New study pinpoints source of impulsive behavior," Katherine Hunt, Reuters News Service, May 21, 2001.
"Brain: instant gratification center found?" Jonathan Trout, Nature (online), May 25, 2001, http://www.nature.com.