Ketamine is a rapid-acting antidepressant associated with various cognitive side effects. To mitigate these side effects while enhancing efficacy, it can be co-administered with other antidepressants. In our study, we adopted a similar strategy by combining ketamine with environmental enrichment, a potent sensory-motor paradigm, in adult male Wistar rats. We divided the animals into four groups...
The gut-brain axis, which includes gut microbiota and microbiome-derived metabolites, might be implicated in depression. We reported the sustained prophylactic effects of a new antidepressant arketamine in chronic restrain stress (CRS) model of depression. In this study, we investigated the role of gut-brain axis on the prophylactic effects of arketamine in the CRS (7 days) model. Pretreatment...
Psychedelic drugs, which share in common 5-HT2A receptor agonist activity, have shown promise in treating alcohol-use disorders (AUDs). Repeated exposure to ethanol (EtOH) induces molecular and behavioural changes reflective of neuroadaptations that may contribute to addiction. Psychedelic drugs can induce neuroplasticity also, raising the possibility that their potential clinical effects in...
Anesthetic ketamine and classical psychedelics that act as 5-hydroxytryptamine-2A receptor (5-HT2AR) agonists demonstrated rapid and sustained antidepressant actions in patients with treatment-resistant depression. The new antidepressant arketamine is reported to cause long-lasting prophylactic effects in lipopolysaccharide (LPS)-treated mice and mice exposed to chronic restrain stress (CRS)....
Major depressive disorder (MDD) is a debilitating illness that affects millions of people worldwide. Currently available antidepressants often take weeks to months to reach their full effect, which leads to an increased risk of suicidal behavior in patients with MMD. Intranasally, esketamine has emerged as an alternative to current antidepressants because of its rapid onset and long-lasting...
Ketamine is a noncompetitive N-methyl-d-aspartate (NMDA) receptor antagonist with antidepressant, anxiolytic, and memory effects in clinical and preclinical studies. The present studies investigated the behavioral effects of ketamine in animals exposed to a consummatory successive negative contrast (cSNC) task involving unexpected reward downshift, negative emotion (frustration), and aversive...
Fatty acid binding protein 5 (FABP5) interacts with the endocannabinoid system in the brain via intracellular transport of anandamide, as well as Δ9-tetrahydrocannabinol (THC), the main psychoactive component of cannabis. Previous work has established the behavioral effects of genetic deletion of FABP5, but not in the presence of THC. The present study sought to further elucidate the role of...
The co-use of nicotine and cannabis has been steadily rising in the United States. Rodent studies suggest that delta-9-tetrahydrocannabinol (THC) could increase addictive qualities of nicotine, but whether repeated THC exposure alters self-administration of nicotine has not been tested. We hypothesized that THC would increase the reinforcing effects of nicotine and alter nicotine intake. Adult...
Schizophrenia is a chronic, debilitating mental illness that has not yet been completely understood. In this study, we aimed to investigate the effects of different doses of ketamine, a non-competitive NMDA receptor antagonist, on the positive- and negative-like symptoms of schizophrenia. We also explored whether these effects are related to changes in the immunoreactivity of GAD67, TH, and...
Ketamine has been increasingly used as a rapid-onset antidepressant in specific clinical settings. However, as a psychedelic reagent, the potential of physical and psychological dependence limits its clinical use. Here, we added retigabine, a KCNQ channel opener, as an adjunctive treatment to observe its effect on ketamine's antidepressant property in a forced swim test in both male and female...
N-methyl-d-aspartate receptor (NMDAR) antagonist antidepressants have known potential for abuse liability. The aim of this study was to evaluate the abuse liability of D-cycloserine (DCS), using a self-administration paradigm in which DCS was tested for its efficacy in substituting for ketamine in ketamine-dependent rats. A standard intravenous self-administration study was conducted in male...
Initiation of non-medical dextromethorphan (DXM) use often occurs in adolescence, yet little is known about the consequences when use begins during this developmental period. The current experiments examined the acute response and the effects of repeated exposure to DXM in adolescence on behavior in adulthood. We examined locomotor activity, locomotor sensitization, and cognitive function, in...
Prefrontal and striatal glutamate plays an important role in modulating striatal dopamine levels and an imbalance in regional glutamate has been identified in several psychiatric conditions. We hypothesized that this imbalance also exists in cannabis use disorder (CUD). We recently quantified the difference in glutamate of dorsal anterior cingulate (dACC) and striatum regions in the...
Major depression (MDD) is a serious neuropsychiatric disorder afflicting around 16-17 % of the global population and is accompanied by recurrent episodes of sadness and suicidal thoughts. Current pharmacological interventions take several weeks to even months for an improvement in depressive symptoms to emerge, with a significant percentage of individuals not responding to these medications at...
Approximately two-thirds of patients with major depressive disorder (MDD) fail to respond to conventional antidepressants, suggesting that additional mechanisms are involved in the MDD pathophysiology. In this scenario, the glutamatergic system represents a promising therapeutic target for treatment-resistant depression. To our knowledge, this is the first study using semantic approach with...
The behavioral effects of cannabidiol (CBD) are understudied, but are important, given its therapeutic potential and widespread use as a natural supplement. The objective of this study was to test whether a single injection of CBD affected anxiety-like or attention-like behavior, or memory in wildtype mice or mice with reported trait anxiety due to a targeted gene-deletion in a...
Classical psychedelics with 5-hydroxytryptamine-2A receptor (5-HT2AR) agonism have rapid antidepressant actions in patients with depression. However, there is an ongoing debate over the role of 5-HT2AR in the antidepressant-like actions of psychedelics. In this study, we compared the effects of DOI (2,5-dimethoxy-4-iodoamphetamine: a hallucinogenic psychedelic drug with potent 5-HT2AR agonism),...
Schizophrenia is a chronic disabling disease affecting 1 % of the population. Current antipsychotics have limited efficacy in mitigating the severity of the symptoms of the disease. Therefore, searching for new therapeutic targets is essential. Previous studies have shown that α2C-adrenoceptor antagonists may have antipsychotic and pro-cognitive effects. Therefore, the current study evaluates...
Polydrug use is well documented in synthetic cathinone users, although the consequences of such use are not well characterized. In pre-clinical research, a pre-exposure to a drug has been reported to attenuate the aversive effects of other drugs which has implications for their abuse potential. The goal of the present study was to investigate the impact of pre-exposure to the synthetic...
MGlu2/3 receptor antagonists produce antidepressant-like effects in animal models of depression. A number of mechanisms responsible for these actions are convergent to the mechanism of the fast antidepressant-like effect of ketamine. Furthermore, the data indicate that ketamine effect is related to the action of mGlu2 receptors and may be reduced by their agonists. The above facts became the...
Dissociative-based new psychoactive substances (NPSs) are increasingly available through the Internet, and public health problems related to the recreational use of these substances have been increasing globally. Two such NPSs are deschloroketamine and diphenidine, which are primarily used recreationally as ketamine substitutes. However, there is little scientific evidence to describe the...
Impairments in auditory information processing in schizophrenia as indexed electrophysiologically by P300 deficits during novelty (P3a) and target (P3b) processing are linked to N -methyl- D -aspartate receptor (NMDAR) dysfunction. This study in 14 healthy volunteers examined the effects of a subanesthetic dose of the NMDAR antagonist ketamine on P300 and their relationship to psychomimetic...
Interest in developing minimal side-effect NMDA receptor antagonists for neurological and psychiatric disorders has been energized by the recent introduction of esketamine into clinical practice for treatment-resistant depression. Structural analogs of dextromethorphan bind with low affinity to the NMDA receptor ion channel, have functional effects in vivo, and generally display a lower...
Adolescence is a period of profound developmental changes, which run the gamut from behavioral and neural to physiological and hormonal. It is also a time at which there is an increased propensity to engage in risk-taking and impulsive behaviors like drug use. This review examines the human and preclinical literature on adolescent drug use and its consequences, with a focus on dissociatives...
Ketamine, a dissociative anaesthetic, has been used in the treatment of major depressive disorder (MDD) as a rapid acting antidepressant drug. Recent studies have shown that ketamine may increase the potential risk of treatment-induced mania in MDD patients. Lithium is a well-known mood stabilizer and has been widely used for the treatment of mania. It is not fully understood which forebrain...