Progress in neuro-psychopharmacology & biological psychiatry
December 20, 2022
John Cook, Angelos Halaris
Esketamine, approved by the FDA in early 2019 for treatment resistant depression, works by blocking NMDA receptors and improving symptoms rapidly through glutamatergic activation. Widespread use is limited by concerns about durability of response, especially during maintenance. Since esketamine must be taken with an oral antidepressant, choosing the right combination may improve outcomes. Because many patients with major depressive disorder and treatment resistant depression have dysfunction in dopaminergic pathways, adding a prodopaminergic agent like bupropion could enhance and prolong response. Anecdotal evidence and mechanistic rationale support this approach, and the oral combination of dextromethorphan and bupropion (AXS-05) has shown promise in clinical trials. This paper argues that dopaminergic enhancement may boost esketamine's efficacy and durability, encouraging further research.
Progress in neuro-psychopharmacology & biological psychiatry
January 10, 2021
Hanna J Szkudlarek, Mar Rodríguez-ruiz, Roger Hudson et al.
In rats, THC infused directly into the medial prefrontal cortex (PFC) caused strong panic-like responses, while CBD did not affect panic but blocked the formation of associative fear memories and impaired latent inhibition and oddity discrimination. CBD counteracted THC-induced panic and prevented THC-driven phosphorylation of ERK1/2. CBD's effects on perception and latent inhibition depended on 5-HT1A receptor transmission and were accompanied by reduced phosphorylation of p70S6K, independently of THC. The findings suggest dissociable molecular mechanisms: THC promotes panic via ERK1/2 phosphorylation, while CBD impairs perceptive functions via 5-HT1A receptors and reduced p70S6K phosphorylation.
Progress in neuro-psychopharmacology & biological psychiatry
November 3, 2016
Ralf-Peter Behrendt
Hallucinations may not be fundamentally different from normal conscious experiences; both arise from the same neural processes. Conscious experience reflects the formation of event (episodic) memories, linking hallucinations to the hippocampus. Perceptions and misperceptions are manifestations of activity patterns that recurrently emerge in the CA3 network of the hippocampus, which forms allocentric representations of objects in context. The hippocampus integrates sensory information, emotional context, and guides decision-making via the medial prefrontal cortex. Disruptions in relational memory processing in the hippocampus can give rise to hallucinations. Neurobiological and neuroimaging findings in schizophrenia research support this framework.
Progress in neuro-psychopharmacology & biological psychiatry
October 1, 2015
Andrea De Bartolomeis, Francesco Errico, Giuseppe Aceto et al.
Elevated D-aspartate levels in mice altered expression of key postsynaptic density genes involved in glutamate signaling. In mice lacking D-aspartate oxidase (Ddo-/-), which have persistently high brain D-aspartate, Homer1a expression decreased in the prefrontal cortex, Homer1b/c increased in the striatum, and PSD-95 decreased in both striatum and cortex. Acute treatment with phencyclidine (PCP) restored and even potentiated Homer1a expression in the prefrontal cortex of these mutant mice but had limited effects on other genes. These findings suggest that sustained D-aspartate elevation may trigger adaptive changes in Homer1a that could explain protective effects against PCP-induced behavioral alterations.
Progress in neuro-psychopharmacology & biological psychiatry
July 3, 2014
Colm M P O'Tuathaigh, Ilse Gantois, John L Waddington
Cannabis use increases the risk of developing schizophrenia and related psychotic disorders. Factors such as age at first cannabis use, genetic predisposition, and other environmental risks may influence susceptibility. Genetic studies increasingly implicate genes involved in dopamine signaling in the link between cannabis and psychosis. This review examines human and animal research on the neural basis of these interactions. More studies are needed to understand the long-term and neurodevelopmental effects of cannabis use, which could clarify the cannabis-psychosis relationship.
Progress in neuro-psychopharmacology & biological psychiatry
February 15, 2008
Mikhail Kalinichev, Melanie J Robbins, Elizabeth M Hartfield et al.
In a rat model of acute psychosis induced by phencyclidine (PCP), the drug's effects on movement and gene expression depend on how it is given. Adult male rats received PCP either injected into the abdomen or under the skin. PCP given under the skin produced stronger and longer-lasting hyperactivity, higher drug levels in blood and brain, and greater activation of several immediate early genes in the prefrontal cortex compared to injection into the abdomen. The differences in drug concentration appeared within 30 minutes and lasted up to 4 hours. The subcutaneous route provides a more robust and consistent model for studying acute psychosis.
Progress in neuro-psychopharmacology & biological psychiatry
January 1, 1990
P Popoli, A Pezzola, A Scotti de Carolis
Clonidine, an alpha-2 adrenergic agonist, caused sedation and synchronized brain electrical activity in rats starting at 0.05 mg/kg. At low and moderate doses of the dissociative anesthetics PCP and ketamine, clonidine fully inhibited their EEG and behavioral effects, but at high doses it potentiated them. Yohimbine reversed both the inhibitory and potentiating effects of clonidine, as well as the sedation and EEG synchronization. Prazosin did not produce these effects, indicating alpha-2 adrenoceptors are involved. The interaction between dissociative anesthetics and central adrenergic receptors appears complex, with possible relevance for improving ketamine anesthesia and treating PCP intoxication.