Electrical stimulation of the ventral tegmental area restores consciousness from sevoflurane-, dexmedetomidine-, and fentanyl-induced unconsciousness in rats.

Background: Dopaminergic neurons in the ventral tegmental area (VTA) are crucially involved in regulating arousal, making them a potential target for reversing general anesthesia. Electrical deep brain stimulation (DBS) of the VTA restores consciousness in animals anesthetized with drugs that primarily enhance GABA receptors. However, it is unknown if VTA DBS restores consciousness in animals anesthetized with drugs that target other receptors.

Return of the Righting Reflex Does Not Portend Recovery of Cognitive Function in Anesthetized Rats.

As the number of individuals undergoing general anesthesia rises globally, it becomes increasingly important to understand how consciousness and cognition are restored after anesthesia. In rodents, levels of consciousness are traditionally captured by physiological responses such as the return of righting reflex (RORR). However, tracking the recovery of cognitive function is comparatively difficult.

Stability of extemporaneously prepared preservative-free methylphenidate 5 mg/mL intravenous solution.

Purpose: To advance the implementation of consciousness-promoting therapies in patients with acute disorders of consciousness, the availability of potential therapeutic agents in formulations suitable for administration in hospitalized patients in the presence of complex comorbid conditions is paramount. The purpose of this study is to evaluate the long-term stability of extemporaneously prepared preservative-free methylphenidate hydrochloride (HCl) 5 mg/mL intravenous solution for experimental use.

Methods: A methylphenidate 5 mg/mL solution was prepared under proper aseptic techniques with Methylphenidate Hydrochloride, USP, powder mixed in sterile water for solution.

D-Amphetamine Rapidly Reverses Dexmedetomidine-Induced Unconsciousness in Rats.

D-amphetamine induces emergence from sevoflurane and propofol anesthesia in rats. Dexmedetomidine is an α-adrenoreceptor agonist that is commonly used for procedural sedation, whereas ketamine is an anesthetic that acts primarily by inhibiting NMDA-type glutamate receptors. These drugs have different molecular mechanisms of action from propofol and volatile anesthetics that enhance inhibitory neurotransmission mediated by GABA receptors.

The Neural Circuits Underlying General Anesthesia and Sleep.

General anesthesia is characterized by loss of consciousness, amnesia, analgesia, and immobility. Important molecular targets of general anesthetics have been identified, but the neural circuits underlying the discrete end points of general anesthesia remain incompletely understood. General anesthesia and natural sleep share the common feature of reversible unconsciousness, and recent developments in neuroscience have enabled elegant studies that investigate the brain nuclei and neural circuits underlying this important end point.

Activation of GABAergic Neurons in the Rostromedial Tegmental Nucleus and Other Brainstem Regions Promotes Sedation and Facilitates Sevoflurane Anesthesia in Mice.

Many general anesthetics potentiate gamma-aminobutyric acid (GABA) A receptors but their neuroanatomic sites of action are less clear. GABAergic neurons in the rostromedial tegmental nucleus (RMTg) send inhibitory projections to multiple arousal-promoting nuclei, but the role of these neurons in modulating consciousness is unknown. In this study, designer receptors exclusively activated by designer drugs (DREADDs) were targeted to RMTg GABAergic neurons of Vgat-ires-Cre mice.

D-Amphetamine Accelerates Recovery of Consciousness and Respiratory Drive After High-Dose Fentanyl in Rats.

In the United States, fentanyl causes approximately 60,000 drug overdose deaths each year. Fentanyl is also frequently administered as an analgesic in the perioperative setting, where respiratory depression remains a common clinical problem. Naloxone is an efficacious opioid antagonist, but it possesses a short half-life and undesirable side effects.

Metabolomics in patients with psychosis: A systematic review.

The purpose of this article is to provide a comprehensive review of metabolomics studies for psychosis, as a means of biomarker discovery. Manuscripts were selected for review if they involved discovery of metabolites using high-throughput analysis in human subjects and were published in the last decade. The metabolites identified were searched in Human Metabolome Data Base (HMDB) for a link to psychosis.