Catecholamine and MHPG plasma levels, platelet MAO activity, and3H-imipramine binding in heroin and cocaine addicts

Abstract

This work evaluated in a population of heroin and heroin plus cocaine human addicts: 1. Norepinephrine (NE), epinephrine (Epi) and 3-methoxy-4-hydroxyphenylglycol (MHPG) (the principal metabolite of brain NE) plasma levels; 2. Monoamine oxidase (MAO) activity; and 3. 3H-imipramine specific binding to the amine carrier in platelets. NE plasma levels were significantly lower in the short-term heroin user groups (1-3 and 4-6 yr), a finding not observed in both long-term heroin user ( > 6 yr) and heroin plus cocaine user ( > 6 yr) groups. Epi levels changed in a similar manner, except that a significant increase was noted in heroin plus cocaine abusers. Conversely, dopamine and MHPG plasma levels increased with the duration of heroin use, and even more with cocaine abuse. Platelet MAO activity increased in all groups. Specific 3H-imipramine binding sites showed an increase after 3 yr of heroin abuse and in all heroin plus cocaine addicts. In conclusion, short-term use of heroin decreases NE or Epi release, but with prolonged use, a slow adaptation occurs. In contrast, cocaine inhibits the neuronal Epi uptake, even in a situation of long duration of abuse. Probably the amine levels additionally regulate the amine carrier, resulting in changes that show a different pattern from major depression. These drugs of abuse may also influence directly or indirectly related enzymatic systems.

Substance use modulates stress reactivity: Behavioral and physiological outcomes

“…Heroin and cocaine addicts both exhibit an increase in plasma levels of norepinephrine that parallels their duration of use [93]. A similar increase in plasma norepinephrine is seen in recently abstinent alcoholics compared to healthy controls in response to a yohimbine challenge [94] (which increases norepinephrine release by blocking alpha-2 adrenergic receptors [95]).…”

Treatment of patients with cocaine‐induced arrhythmias: bringing the bench to the bedside

“…Increased circulating catecholamine concentrations likely result from blockade of their re-uptake and increased release from central nervous system stimulation [5,46,47]. This typically produces supraventricular rhythms, most commonly sinus tachycardia but also re-entrant supraventricular tachycardia and atrial fibrillation.…”

“…First, cocaine increases concentrations of circulating catecholamines [5] which typically increase heart rate. Since sodium channel blockade follows use-dependent kinetics, increases in heart rate exacerbate sodium channel blockade.…”

Differences in platelet serotonin transporter sites between African-American tobacco smokers and non-smokers

“…Indirect evidence implicating the 5HTT in nicotine dependence comes from studies of substance abusing individuals. Changes in platelet tritiated imipramine or paroxetine binding have been reported in alcoholics (Patkar et al 1995), heroin abusers (Macedo et al 1995), and cocaine abusers (Patkar et al 2003). Furthermore, in addition to nicotine, other constituents of tobacco smoke may also be associated with altered serotonergic function.…”