Psychopharmacology
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Comparative Study
Toluene exposure during the brain growth spurt reduces behavioral responses to noncompetitive N-methyl-D-aspartate receptor antagonists in adult rats.
Toluene exposure during brain growth spurt has been shown to elevate the seizure susceptibility induced by N-methyl-D: -aspartate (NMDA). In the present study, behavioral responses to NMDA antagonists were studied to determine whether neonatal toluene exposure produces residual deficits in the NMDA glutamatergic system controlling behaviors. We also investigated if the effect of toluene exposure depends strongly on the developmental stage. ⋯ These results indicate that neonatal but not adolescent toluene exposure produces long-term effects on selective behaviors induced by NMDA antagonists. Theses findings further support the hypothesis that functional changes in NMDA receptors may be related to the neurobehavioral dysfunction associated with fetal solvent syndrome.
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Comparative Study
Anti-nociception is selectively enhanced by parallel inhibition of multiple subtypes of monoamine transporters in rat models of persistent and neuropathic pain.
Neuropathic pain is characterised by hyperexcitability within nociceptive pathways that manifests behaviourally as allodynia and hyperalgesia and remains difficult to treat with standard analgesics. However, antidepressants have shown reasonable preclinical and clinical anti-nociceptive efficacy against signs and symptoms of neuropathic pain. ⋯ Combined re-uptake inhibition of 5-HT and NA appears to confer a greater degree of anti-nociception in animal models of experimental pain than single mechanism of action inhibitors. The selective attenuation of mechanical allodynia by bupropion suggests that the additional re-uptake of DA may further augment 5-HT/NA re-uptake mediated anti-nociception after nerve injury.
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Several reports have suggested the involvement of brain adenosine and dopamine receptors in different actions produced by ethanol such as motor incoordination or anxiolytic, hypnotic and reinforcing effects. The co-localization and interaction between adenosine and dopamine receptors in different brain regions has also been well documented. However, few studies have demonstrated the involvement of these mechanisms in the tolerance induced by ethanol. ⋯ Our results suggest that the rapid tolerance to ethanol-induced motor impairment in mice may be modulated by adenosine A1 receptors and dopamine D1 receptors.
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Randomized Controlled Trial
Does modafinil activate the locus coeruleus in man? Comparison of modafinil and clonidine on arousal and autonomic functions in human volunteers.
Modafinil is a wakefulness-promoting drug which is likely to activate some wakefulness-promoting and/or inhibit sleep-promoting neurones in the brain. The locus coeruleus (LC) is a wakefulness-promoting noradrenergic nucleus whose activity can be "switched off" by the alpha2-adrenoceptor agonist clonidine, leading to sedative and sympatholytic effects. ⋯ Clonidine exerted sympatholytic and sedative effects, whereas modafinil had sympathomimetic and some alerting effects. Modafinil may activate noradrenergic neurones in the LC involved in arousal and pupillary control, without affecting extracoerulear noradrenergic neurones involved in cardiovascular and salivary regulation.
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Controlled Clinical Trial
Reinforcing effects of oral Delta9-THC in male marijuana smokers in a laboratory choice procedure.
Oral Delta-9-tetrahydrocannabinol (Delta(9)-THC; Marinol) is medically available for the treatment of nausea associated with cancer chemotherapy and for wasting syndromes related to HIV/AIDS. Little is known about its reinforcing effects. ⋯ These data indicate that oral Delta(9)-THC may have modest abuse liability in experienced marijuana smokers.