SynapseMay 1, 2026Bridget Xu, Cassandra Carrasco, Yi‐Wen Chen et al.
ABSTRACT Anorexia nervosa is a deadly eating disorder marked by extreme food restriction, compulsive exercise, and severe weight loss. In a prior study using the activity‐based anorexia (ABA) animal model of anorexia nervosa, 30 mg/kg, but not 3 mg/kg, of ketamine reduced relapse vulnerability, measured as increased food intake, increased body weight (BW), and reduced excessive wheel running,...
SynapseNovember 1, 2025Oliver H Miller, Nils Grabole, Isabelle Wells et al.
Low-dose ketamine is an efficacious antidepressant for treatment-resistant unipolar and bipolar depressed patients. Major depressive disorder patients receiving a single infusion report elevated mood within 2 h, and ketamine's antidepressant effects have been observed as long as 7 days posttreatment. In light of this remarkable observation, efforts have been undertaken to "reverse-translate"...
Psychedelic compounds have gained renewed interest due to their rapid and long-lasting therapeutic effects on stress-related disorders. While the underlying mechanisms of therapeutic actions of psychedelic compounds are still unclear, these drugs are thought to modulate the activity of the serotonergic system, primarily through activating serotonin type 2A receptor (5-HT2AR) and studies have...
Anorexia nervosa (AN) is an eating disorder with the second highest mortality of all mental illnesses and high relapse rate, especially among adult females, yet with no accepted pharmacotherapy. A small number of studies have reported that adult females who struggled with severe and relapsing AN experienced sustained remission of the illness following ketamine infusions. Two other reports...
SynapseJuly 1, 2024Simone Larsen Bærentzen, Jakob Borup Thomsen, Majken Borup Thomsen et al.1 citation
Major depressive disorder is one of the most prevalent mental health disorders, posing a global socioeconomic burden. Conventional antidepressant treatments have a slow onset of action, and 30% of patients show no clinically significant treatment response. The recently approved fast-acting antidepressant S-ketamine, an N-methyl-D-aspartate receptor antagonist, provides a new approach for...
Anorexia nervosa (AN) is a mental illness with the highest rates of mortality and relapse, and no approved pharmacological treatment. Using an animal model of AN, called activity‐based anorexia (ABA), we showed earlier that a single intraperitoneal injection of ketamine at a dose of 30 mg/kg (30mgKET), but not 3 mg/kg (3mgKET), has a long‐lasting effect upon adolescent females of ameliorating...
SynapseOctober 2021Kyle A Windisch, Sanoara Mazid, Megan A Johnson et al.
Our prior studies demonstrated that the rat hippocampal opioid system can undergo sex-specific adaptations to external stimuli that can influence opioid-associated learning processes. This opioid system extensively overlaps with the cannabinoid system. Moreover, acute administration of Δ9 Tetrahydrocannabinoid (THC), the primary psychoactive constituent of cannabis, can alter cognitive...
SynapseMay 1, 2019Sharon Thomson, Bailey Dyck, Ritesh Daya et al.
Abstract: Schizophrenia is a mental disorder characterized by positive symptoms, negative symptoms, and cognitive dysfunction. Phencyclidine (PCP)—a N‐methyl‐D‐aspartate (NMDA) receptor antagonist—induces symptoms indistinguishable from those of schizophrenia. A reduction of the phosphoprotein synapsin II has also been implicated in schizophrenia and has a well‐known role in the maintenance of...
SynapseApril 2018Benjamin B Tournier, Andrea Dimiziani, Stergios Tsartsalis et al.
The Roman high (RHA)- and low (RLA)-avoidance rat sublines have been identified as an addiction-prone and addiction-resistant phenotype based on their high vs. low locomotor responsiveness to novelty and high vs. low ability to develop neurochemical and behavioral sensitization to psychostimulants, respectively. Most studies though have focused on psychostimulants and little is known about the...
SynapseMarch 2018Bryan Kolb, Yilin Li, Terry Robinson et al.
Psychoactive drugs have the ability to alter the morphology of neuronal dendrites and spines and to influence later experience-dependent structural plasticity. If rats are given repeated injections of psychomotor stimulants (amphetamine, cocaine, nicotine) prior to being placed in complex environments, the drug experience interferes with the ability of the environment to increase dendritic...
SynapseJune 2014Yusuke Katanuma, Tadahiro Numakawa, Naoki Adachi et al.
Downregulation of brain-derived neurotrophic factor (BDNF), a member of neurotrophin family, has been implicated in psychiatric diseases including schizophrenia. However, detailed mechanisms of its reduction in patients with schizophrenia remain unclear. Here, using cultured cortical neurons, we monitored BDNF mRNA levels following acute application of phencyclidine [PCP; an...
3,4-Methylenedioxymethamphetamine (MDMA)'s O-demethylenated metabolite, 3,4-dihydroxymethamphetamine (HHMA), has been hypothesized to serve as a precursor for the formation of toxic catechol-thioether metabolites (e.g., 5-N-acetylcystein-S-yl-HHMA) that mediate MDMA neurotoxicity. To further test this hypothesis, HHMA formation was blocked with dextromethorphan (DXM), which competitively...
A number of published studies have questioned the serotonin neurotoxic potential of 3,4-methylenedioxymethamphetamine (MDMA, "ecstasy") and related drugs (fenfluramine, p-chloroamphetamine) based upon results from Western blot studies using a custom synthesized serotonin transporter (SERT) antibody that found no reduction in the abundance of a 50kDa protein after substituted amphetamine...
SynapseFebruary 2011Sherry M Zakhary, Diana Ayubcha, Farah Ansari et al.
Ketamine exerts powerful anesthetic, psychotic, and antidepressant effects in both healthy volunteers and clinically depressed patients. Although ketamine targets particular glutamate receptors, there is a dearth of evidence for additional, alternative molecular substrates for the behavioral actions of this N-methyl-D-aspartate (NMDA) receptor antagonist drug. Here, we provide behavioral and...
(+)‐Methamphetamine (MA), (±)‐3,4‐methylenedioxymethamphetamine (MDMA), (+)‐amphetamine (AMPH), and (±)‐fenfluramine (FEN) are phenylethylamines with CNS effects. At higher doses, each induces protracted reductions in brain dopamine (DA) and/or serotonin. Chronic MA and MDMA users show persistent monoamine reductions and cognitive impairments. In rats, similar neurochemical effects can be...
Repeated intermittent methylenedioxymethamphetamine exposure protects against the behavioral and neurotoxic, but not hyperthermic, effects of an MDMA binge in adult rats.
Abstract MDMA (3,4‐Methylenedioxymethamphetamine) is an amphetamine derivative widely used for recreational purposes. We have recently shown that repeated treatment with high doses of MDMA‐induced impairments in the acquisition and recall of an active avoidance task in mice. In this study, we examined whether the endogenous peroxisome proliferator‐activated receptor‐α (PPAR‐α) agonist,...
Although it is commonly stated that phencyclidine is an antagonist at ionotropic glutamate receptors, there has been little measure of its potency on other receptors in brain tissue. Although we previously reported that phencyclidine stimulated cloned-dopamine D2Long and D2Short receptors, others reported that phencyclidine did not stimulate D2 receptors in homogenates of rat brain striatum....
It has previously been reported that the glutamate ionotropic antagonist phencyclidine directly inhibits the release of prolactin in anterior pituitary cells in culture, suggesting that phencyclidine has a dopamine (DA)-like action on prolactin-releasing cells. It has also been reported that the glutamate metabotropic agonist LY379268 can stimulate the incorporation of [35S]GTP-gamma-S into DA...
Abstract The amphetamine analogue 3,4‐methylenedioxymethamphetamine (MDMA or “Ecstasy”) is a popular drug of abuse which causes different neurotoxic effects in the mouse compared with the rat. In mice, MDMA produces damage to striatal dopamine terminals, having little long‐term effects on serotonin (5‐HT) containing neurons. A relevant feature of the striatum is its striosome/matrix...
18-Methoxycoronaridine (18-MC), a novel iboga alkaloid congener, is a potential treatment for drug addiction. 18-MC has been shown to decrease self-administration of drugs (e.g., morphine, methamphetamine, nicotine) and attenuate opioid withdrawal in rats. In previous studies, systemic pretreatment with 18-MC abolished the sensitized increase in accumbens dopamine levels induced by chronic...
Abstract The psychostimulant 3,4‐methylendioxymethamphetamine (MDMA, “ecstasy”) evokes degeneration of telencephalic serotonin innervations in rodents, nonhuman primates, and human recreational drug users. However, there has been no alternative to nonhuman primates for studies of the cognitive and neurochemical consequences of serotonin depletion in a large‐bodied animal. Therefore, we used...
SynapseJuly 1, 2006Juan Liu, Toshihito Suzuki, Tatsunori Seki et al.
Dysfunctional maturation of neural networks, particularly hippocampus-prefrontal networks, may be of particular interest in determining the pathophysiology of schizophrenia. Phencyclidine (PCP)-induced symptoms in humans appear to offer a more complete model of schizophrenia than do amphetamine-induced symptoms. This study investigated the effects of intermittent i.p. injections of PCP (7.5...
Although the psychotomimetic action of phencyclidine is often used to model a hypoglutamate theory of psychosis or schizophrenia, work also exists showing that phencyclidine has a significant affinity for the dopamine D2 receptor. The present study was done to determine whether phencyclidine has a direct functional dopamine-like action on cells. The effect of phencyclidine was tested on the...
Salvinorin A, a potent hallucinogen isolated from the leaves of Salvia divinorum, has gained popularity among adolescents in the USA. No detailed study of the pharmacokinetics has been conducted in vivo. The present study investigates the in vivo pharmacokinetics of salvinorin A (0.032 mg/kg, i.v. bolus) in rhesus monkeys (n=4, 2 male, 2 female). The elimination t(1/2) was rapid (56.6+/-24.8...