Psychopathic traits modulate brain responses to drug cues in incarcerated offenders

Recent neuroscientific evidence indicates that psychopathy is associated with abnormal function and structure in limbic and paralimbic areas. Psychopathy and substance use disorders are highly comorbid, but clinical experience suggests that psychopaths abuse drugs for different reasons than non-psychopaths, and that psychopaths do not typically experience withdrawal and craving upon becoming incarcerated. These neurobiological abnormalities may be related to psychopaths\u27 different motivations for-and symptoms of-drug use. This study examined the modulatory effect of psychopathic traits on the neurobiological craving response to pictorial drug stimuli. Drug-related pictures and neutral pictures were presented and rated by participants while hemodynamic activity was monitored using functional magnetic resonance imaging. These data were collected at two correctional facilities in New Mexico using the Mind Research Network mobile magnetic resonance imaging system. The sample comprised 137 incarcerated adult males and females (93 females) with histories of substance dependence. The outcome of interest was the relation between psychopathy scores (using the Hare Psychopathy Checklist-Revised) and hemodynamic activity associated with viewing drug-related pictures vs. neutral pictures. There was a negative association between psychopathy scores and hemodynamic activity for viewing drug-related cues in the anterior cingulate, posterior cingulate, hippocampus, amygdala, caudate, globus pallidus, and parts of the prefrontal cortex. Psychopathic traits modulate the neurobiological craving response and suggest that individual differences are important for understanding and treating substance abuse

Disposition and Metabolism of 1-Nitropropane in Rats and Chimpanzees.

The metabolic fate of 1-nitropropane (1-NP) has not been previously reported. In this study male rats and chimpanzees were given single doses of 40 mg/kg ip and 5 mg/kg iv 1-[1-14C]NP, respectively. The quantitative extent of urinary and fecal elimination was similar in both species. The rats excreted 16.5% of the dose in urine and 1.7% in feces. For chimpanzees the respective values were 14.8 and 1.2%. Experiments with rats demonstrated that the major route of elimination was by exhalation. With a total elimination via the lungs of 72.6%, rats expired 10.3% of the dose as unchanged 1-NP. Five polar metabolites were isolated from the urine of chimpanzees. The two major metabolites were identified as 3-hydroxypropionic acid and N-methyl-N-2-(methylsulfinyl)ethylpropionic acid amide (NMPA). Both substances were also excreted in rat urine. The two identified metabolites indicate that 1-NP was degraded to propionic acid, part of which was modified to 3-hydroxypropionic acid or NMPA. A hypothetical pathway for the biochemical generation of NMPA is suggested

Effects of short-term inhalation exposure to 1-nitropropane and 2- nitropropane on rat liver enzymes.

Male Sprague-Dawley rats were exposed to vapors of 1-nitropropane (1-NP) and 2-nitropropane (2-NP) at air concentrations of 100 ppm for 7 hours per day on four consecutive days. Livers were analyzed for enzymatic activities after 1-, 2-, and 4-day inhalation periods. Liver microsomal cytochrome P450 was depressed by 2-NP and elevated following exposure to 1-NP. Levels of cytochrome b5 were slightly increased in rats exposed to 1-NP and remained unchanged after inhalation of 2-NP. Total glutathione (GSH), GSH S- transferase, and UDP-glucuronosyltransferase activities were enhanced by 2- NP. 1-NP induced GSH peroxidase while 2-NP did not. Glutathione reductase was not altered after exposure to either isomer. No changes in the microsomal malondialdehyde content as a measure of lipid peroxidation and in the levels of serum aspartate transferase and serum glutamic oxaloacetic transaminase were observed during a 4-day exposure period in either of the exposed groups compared to control animals

Nitroreduction is not Involved in the Genotoxicity of 2-nitropropane in Cultured Mammalian Cells.

We have investigated the importance of nitroreduction for the genotoxicity of the carcinogen 2-nitropropane (2-NP) in primary cultures of rat hepatocytes and in V79 Chinese hamster cells. Induction of DNA repair synthesis was used as an indicator of genotoxic effects in hepatocytes. Genotoxicity in V79 cells was determined as induction of DNA repair, micronuclei and mutations to 6-thioguanine (TG) resistance. Both hepatocytes and V79 cells were found capable of reducing and oxidizing 2-NP. Reduction of 2-NP was indicated by the formation of acetone oxime, the tautomeric form of 2-nitrosopropane, the first reduction product of 2-NP. Oxidation of 2-NP was indicated by the production of acetone and nitrite. 2-NP strongly elicited repair in hepatocytes, but acetone oxime and the products of a possible further nitroreduction, isopropyl hydroxylamine (IPHA) and 2-aminopropane did not. None of the reduction products caused repair synthesis in V79 cells. However, in these cells IPHA and 2-NP increased the frequency of TG-resistant mutants. IPHA also markedly induced micronuclei. This was not seen with 2-NP. Acetone oxime was not genotoxic in V79 cells. The observations suggest that reduced metabolites are responsible neither for the induction of DNA repair synthesis by 2-NP in hepatocytes nor for the induction of gene mutations by 2-NP in V79 cells

Fate of two Phenylbenzoylurea Insecticides in an Algae Culture System (Scenedesmus Subspicatus).

The bioaccumulation, elimination and degradation of 14C-labelled diflubenzuron (DFB) and of 1-(2-chlorobenzoyl)-3-(4-chlorophenyl)urea (CCU) was studied in a laboratory algae culture system of scenedesmus subspicatus. Algae were exposed at an initial concentration of 200 μg/l for seven days. Neither substance had an inhibitory effect on the growth of algae. The half life of DFB and CCU was 3 and 1 days, respectively, as measured by HPLC. The distribution of 14C between medium and algae was measured. In the case of DFB radioactivity in algae increased steadily and levelled off at approximately 60% after 5 days. Due to algae growth BCF values decreased from 4310 to 889 for DFB and from 6719 to 304 for CCU during the exposure period. The relationship between algae density and bioconcentration could be correlated by an adsorption isotherm. Elimination of both compounds was rapid during the first hours

FATE OF 2 PHENYLBENZOYLUREA INSECTICIDES IN AN ALGAE CULTURE SYSTEM (SCENEDESMUS-SUBSPICATUS)

The bioaccumulation, elimination and degradation of C-14-labelled diflubenzuron (DFB) and of 1-(2-chlorobenzoyl)-3-(4-chlorophenyl)urea (CCU) was studied in a laboratory algae culture system of scenedesmus subspicatus. Algae were exposed at an initial concentration of 200 mug/l for seven days. Neither substance had an inhibitory effect on the growth of algae. The half life of DFB and CCU was 3 and 1 days, respectively, as measured by HPLC. The distribution of C-14 between medium and algae was measured. In the case of DFB radioactivity in algae increased steadily and levelled off at approximately 60 % after 5 days. Due to algae growth BCF values decreased from 4310 to 889 for DFB and from 6719 to 304 for CCU during the exposure period. The relationship between algae density and bioconcentration could be correlated by an adsorption isotherm. Elimination of both compounds was rapid during the first hours