Psychopharmacology
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Repeated exposure to psychostimulant drugs causes a long-lasting increase in the psychomotor and reinforcing effects of these drugs and an array of neuroadaptations. One such alteration is a hypersensitivity of striatal activity such that a low dose of amphetamine in sensitized animals produces dorsal striatal activation patterns similar to acute treatment with a high dose of amphetamine. ⋯ A lack of stereotypy in the sensitized group indicates a dissociation of behavioral responses to amphetamine and striatal immediate-early gene activation patterns. The increase in c-fos positive nuclei and shift in the distribution of optical density observed in the nucleus accumbens core suggests recruitment of a new population of neurons during expression of sensitization.
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The development of sensitization to amphetamine (AMPH) is dependent on increases in excitatory outflow from the medial prefrontal cortex (mPFC) to subcortical centers. These projections are clearly important for the progressive enhancement of the behavioral response during drug administration that persists through withdrawal. ⋯ The LH, a region implicated in natural and drug reward processes, may play a role in the development and persistence of sensitization to repeated AMPH through its connections with the mPFC and possibly through its orexin neurons.
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Neurodegenerative changes have been suggested to provide a basis for the pathophysiology of schizophrenia. T-817MA (1-{3-[2-(1-benzothiophen-5-yl) ethoxy] propyl} azetidin-3-ol maleate) is a novel compound with neuroprotective and neurite-outgrowth effects, as elicited in rat primary cultured neurons. ⋯ These results suggest that T-817MA is effective in ameliorating sensorimotor gating deficits caused by chronic PCP treatment, possibly via neuroprotective actions. Our findings provide a novel therapeutic approach for patients with schizophrenia.
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Randomized Controlled Trial
Effects of smoking abstinence on adult smokers with and without attention deficit hyperactivity disorder: results of a preliminary study.
Individuals with attention deficit hyperactivity disorder (ADHD) smoke at higher rates than the general population; however, little is known about the mechanisms underlying this comorbidity. ⋯ This preliminary study is the first to systematically evaluate the effects of acute smoking abstinence in adult smokers diagnosed with ADHD. Individuals with the disorder may smoke at higher rates due to greater worsening of attention and response inhibition after abstinence.
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Group II metabotropic glutamate receptors (mGluRs) comprise the mGluR2 and mGluR3 subtypes, the activation and modulation of which has been suggested to be beneficial for treating schizophrenia. Genetic association studies suggest limited association between mGluR2 and schizophrenia but some association between mGluR3 and schizophrenia. Conversely, pre-clinical studies suggest that mGluR2 may be responsible for mediating the antipsychotic activity of mGluR2/3 agonists, although to date, the role of mGluR3 has not been specifically assessed. ⋯ The mGlu2 but not the mGlu3 receptor subtype mediates the actions of the mGluR2/3 agonist, LY379268, in mouse models predictive of antipsychotic activity.