Aggressive responding of male heroin addicts under methadone treatment: psychometric and neuroendocrine correlates.

Objective measures of experimentally-induced aggressiveness were evaluated in 20 methadone-treated heroin addicts, in comparison to 20 normal healthy male subjects. All the subjects were submitted to preliminary DSM IV interviews, Buss Durkee Hostility Inventory (BDHI) and Minnesota Multiphasic Personality Inventory (MMPI II). During a laboratory task, the point subtraction aggression paradigm (PSAP), subjects earned monetary reinforcers with repeated button presses, and were provoked by the subtraction of money, which was attributed to a fictitious other participants. Subjects could respond by ostensibly subtracting money from the fictitious subject (the aggressive response), or protecting their counter (escape response). Money-earning responses were significantly lower (t=4.38, P<0.001) and aggressive responses significantly higher (t=5.45; P<0.001) in methadone patients in comparison to controls. During the experimentally-induced aggressiveness, plasma adrenocorticotropic hormone (ACTH), cortisol (CORT) and growth hormone (GH) concentrations increased significantly less and norepinephrine (NE) and epinephrine (EPI) levels, together with heart rate (HR), significantly more in methadone subjects than in healthy subjects. PSAP aggressive responses positively correlated with catecholamines changes, BDHI 'direct' and 'irritability' scores, MMPI 'psychopathic deviate' scores both in methadone subjects and controls, and with CORT responses only in healthy subjects. No correlation was found between methadone doses, or exposure extent, and aggressiveness levels. Our findings suggest that heroin dependent patients have higher outward-directed aggressiveness than healthy subjects, in relationship with monoamines hyper-reactivity, also under methadone medication. Aggressiveness in methadone patients seems to be related more to the personality traits than to drug effects. Hypothalamus-pituitary-adrenal (HPA) axis responses, unexpectedly dissociated from catecholamines rise among methadone patients, could be due to a long-lasting inhibitory action exerted by opiates on pro-opio-melanocortin (POMC), or to a premorbid psychobiological condition that exhausted hormonal reactivity.