Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology
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Neuropsychopharmacology · Jul 2013
Nabilone decreases marijuana withdrawal and a laboratory measure of marijuana relapse.
Few individuals seeking treatment for marijuana use achieve sustained abstinence. The cannabinoid receptor agonist, Δ(9)-tetrahydrocannabinol (THC; dronabinol), decreases marijuana withdrawal symptoms, yet does not decrease marijuana use in the laboratory or clinic. Dronabinol has poor bioavailability, which may contribute to its poor efficacy. ⋯ Neither dose condition increased ratings of capsule 'liking' or desire to take the capsules relative to placebo. Thus, nabilone maintenance produced a robust attenuation of marijuana withdrawal symptoms and a laboratory measure of relapse even with once per day dosing. These data support testing of nabilone for patients seeking marijuana treatment.
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Neuropsychopharmacology · Jul 2013
Pain after discontinuation of morphine treatment is associated with synaptic increase of GluA4-containing AMPAR in the dorsal horn of the spinal cord.
Withdrawal from prescribed opioids results in increased pain sensitivity, which prolongs the treatment. This pain sensitivity is attributed to neuroplastic changes that converge at the spinal cord dorsal horn. We have recently reported that repeated morphine administration triggers an insertion of GluA2-lacking (Ca(2+)-permeable) α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptors (AMPAR) in the hippocampus. ⋯ Furthermore, current-voltage relationships of AMPAR-mediated EPSCs showed that rectification index (an indicator of Ca(2+)-permeable AMPAR contribution) is increased in morphine-treated but not in saline-treated mice. These effects could be reversed by infusion of GluA4 antibody through patch pipette. This is the first direct evidence for a role of GluA4-containing AMPAR in morphine-induced pain and highlights spinal GluA4-containing AMPAR as targets to prevent the morphine-induced pain sensitivity.
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Neuropsychopharmacology · Jul 2013
Small-molecule inhibitors at the PSD-95/nNOS interface have antidepressant-like properties in mice.
Previous studies have demonstrated that nitric oxide (NO) synthase inhibitors are as efficacious as tricyclic antidepressants in preclinical antidepressant screening procedures and in attenuating behavioural deficits associated with animal models of depression. The N-methyl-D-aspartate receptor (NMDA-R) complex gates Ca(2+), which interacts with calmodulin to subsequently activate NO synthase. We hypothesised that uncoupling neuronal nitric oxide synthase (nNOS) from the NMDA-R through the scaffolding protein postsynaptic density protein 95 (PSD-95) would produce behavioural antidepressant effects similar to NO synthase inhibitors. ⋯ The antidepressant-like effects of ZL006 also generalise to IC87201 in the TST. IC87201 was devoid of effects on locomotor activity and step-through latency in the passive avoidance cognition test. These data support the hypothesis that targeting the PSD-95/nNOS interaction downstream of NMDA-R produces antidepressant effects and may represent a novel class of therapeutics for major depressive disorders.