Disinhibited, impulsive behavior of, for example, violent offenders, suicidal patients, sensation seekers, and patients with mtisocial personality or substance abuse disorders may involve deficient brain serotonin (5-HT) systems. Brain 5-HT depletion produces disinhibitiodaggression also in experimental animals, as exemplified by the 5-HT depletion-induced anticonflict effect in conflict models, an effect that may reflect anxiolysis and/or poor impulse control (SoubriC. 1986). Pharmacologic manipulations reversing the 5-HT depletioninduced anticonflict effect, such as negative modulators of gamma-aminobutyric acid-a (GABA=)/bcnzodiazepine receptors (see Stkierpalm and Engel, Life Sci 1991;49:139-53). also decrease aggressive and alcohol self-administering behaviors in rats. These similarities may be due to interference in impulse control mechanisms common to the different behavioral models. Naloxone reduces ethanol self-administration, and, using the stable analogue naltrexone. this effect has been confirmed in humans. These findinns and indications of GABA~ antagonistic actions of naloxone prompted us to investigate &e effects of naloxone on 5-HT depletion-induced disinhibitory behaviors, on the expression of c-fos in the amygdala after conflict exposure. and on GABAdbenzodiazepine receptor function in vitro. Naloxone (0.5-5.0 mag, subcutaneously) antagonized the anticonflict effect induced by i.c.v. treatment with the selective 5-HT neurotoxin 5,7-DHT. This effect of naloxone was in turn reversed by a low dose of amobarbital. In a resident-intruder model the number of attacks made by 5,7-DHT-lesioned residents and the total time spent fighting were significantly reduced after pretreatment with naloxone (5.0 mag, subcutaneously) or the partial inverse bedazepine receptor agonist Ro 15-4513 (2.0 mg/kg, orally). Expression of c-fos in the amygdala after conkt exposure was lower in 5.7-DHT-mated rats compared with controls. 'Ibis effect was reversed in the 5-HT-deficient rats after pretreatment with naloxone (5 mag, subcutaneously). Naloxone (0.1-lo00 w) in a concentration-dependent manner counteracted GABA-induced Mcl’ uptake into rat corticohippoc~~al-synaptoneurosomes and shifted the concentration-response curve for GABA-induced C1 uptake to the right (GABA, 3, 10.30, 100 $4, and naloxone, lo00 pM). The naloxone (lo00 @4) effect could be reversed by amobarbital(10-1OOO pM) but not by flumazenil (10-lo00 fl) or morphine (0.1-lo00 pM). These results demonstrate that naloxone has anti-impulsive/anti-aggressive effects that may be mediated via negative modulation of GABAdbenzodiazepine receptor function. Naloxone may alone or in combination with indirect or direct 5-HT receptor agonists represent a new treatment principle for disorders characterized by poor impulse control.