Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology
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Neuropsychopharmacology · May 2005
Neurological and cognitive recovery following abstinence from petrol sniffing.
Anecdotal observations suggest that neurological impairments associated with petrol (gasoline) sniffing resolve with abstinence, although these effects have not been proven empirically. Severe exposure to leaded petrol may induce a lead encephalopathy that extends beyond any acute intoxication and requires emergency hospital treatment. Previously, in chronic petrol sniffers, we showed neurological, saccadic, and cognitive abnormalities that were more severe in petrol sniffers with a history of hospitalization for lead encephalopathy, and that correlated with blood lead levels and the length of time of sniffing petrol. ⋯ The most severe petrol-related neurobehavioral impairment was observed among individuals who had longer histories of abuse and higher blood lead levels, and among petrol sniffers with a history of lead encephalopathy. Those with the greatest extent of neurobehavioral impairment showed the greatest degree of improvement with abstinence, but were less likely to recover completely. This is the first direct evidence that neurological and cognitive impairment from chronic petrol sniffing ameliorates with abstinence and may recover completely.
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Neuropsychopharmacology · Apr 2005
Confirmation of a major QTL influencing oral morphine intake in C57 and DBA mice using reciprocal congenic strains.
C57BL/6 (B6) and DBA/2 (D2) mice exhibit disparate behavior when tested for voluntary morphine intake in a two-bottle choice drinking paradigm with B6 mice consuming 10 times more drug than D2 mice. Previous genetic mapping studies identified a locus, Mop2, on the proximal part of chromosome 10 that explained over half of the genetic variance in this mouse model of opioid self-administration. We constructed a set of reciprocal congenic strains between B6 and D2 mice in which the proximal portion of chromosome 10 has been introgressed from one strain onto the background of the other. ⋯ D2-Mop2 mice was decreased significantly relative to B6 and D2. B6-Mop2 mice. Overall, these data confirm the existence of a gene(s) on chromosome 10 proximal to D10Mit124 that has a strong influence on the difference in morphine drinking behavior between B6 and D2 mice.
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Neuropsychopharmacology · Mar 2005
Comparative Study Clinical Trial Controlled Clinical TrialEffects of the mixed mu/kappa opioid nalbuphine on cocaine-induced changes in subjective and cardiovascular responses in men.
Kappa opioid agonists functionally antagonize some abuse-related and locomotor effects of cocaine, and reduce cocaine self-administration by rhesus monkeys. We compared the cardiovascular and subjective effects of acute doses of the mu/kappa opioid nalbuphine alone (5 mg/70 kg, intravenous (i.v.)), with cocaine alone (0.2 mg/kg, i.v.), and with nalbuphine+cocaine in combination, under placebo-controlled, double-blind conditions. Subjects met American Psychiatric Association Diagnostic and Statistical Manual (DSM-IV) criteria for current cocaine abuse. ⋯ Peak VAS ratings of High, Stimulated, Good Effect, and Drug Effect were also significantly higher after nalbuphine+cocaine than after cocaine alone (p<0.01). Addiction Research Center Inventory (ARCI) scores were equivalent for nalbuphine+cocaine and nalbuphine alone, but the PCAG, MBG, and amphetamine scores were significantly higher after both nalbuphine+cocaine and nalbuphine alone than after cocaine alone (p<0.01-0.003). Thus, there were no additive interactions between nalbuphine and cocaine on cardiovascular, subjective, or drug level measures after acute administration.
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Neuropsychopharmacology · Jan 2005
Direct evidence for the involvement of the mesolimbic kappa-opioid system in the morphine-induced rewarding effect under an inflammatory pain-like state.
Recent clinical studies have demonstrated that when morphine is used to control pain in cancer patients, psychological dependence is not a major concern. The present study was undertaken to ascertain the modulation of psychological dependence on morphine under a chronic pain-like state in rats. The prototypical mu-opioid receptor agonist morphine (8 mg/kg, i.p.) induced a dose-dependent place preference. ⋯ These findings suggest that the inflammatory pain-like state induced by formalin injection may have caused a sustained activation of the kappa-opioidergic system within the N. Acc., resulting in suppression of the morphine-induced rewarding effect in rats. The present study provides further evidence of the clinical usefulness of morphine in patients suffering from severe pain.
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Neuropsychopharmacology · Jan 2005
Randomized Controlled Trial Clinical TrialMu-opioid self-administration vs passive administration in heroin abusers produces differential EEG activation.
Psychoactive drug self-administration (SA) produces different neurobiological effects than passive administration (PA) in non-human animals; however, such consequences have never been examined in human drug abusers. The present study compared electroencephalographic (EEG) activation produced by intravenous PA and SA of the mu-opioid fentanyl in eight heroin-dependent, methadone-stabilized male participants. In phase 1, participants received cumulative PA of fentanyl (up to 1.5 mg/70 kg; session 1), then bolus PA of placebo and fentanyl 1.5 mg/70 kg (session 2). ⋯ In phase 2, bolus fentanyl 1.5 mg/70 kg was available for SA, requiring the participant to complete 1500 responses, in each of two sessions after saline or naloxone pretreatment. Delta EEG peak amplitude increases were greater following fentanyl SA than fentanyl PA, primarily over the central midline region, and were attenuated by naloxone pretreatment. The EEG increase and its attenuation by naloxone agree with preclinical evidence and suggest that SA-related EEG responses were mediated by opioid receptors.