Effects Of Psychoactive Drugs Research Articles

Structural neural plasticity evoked by rapid-acting antidepressant interventions.

A feature in the pathophysiology of major depressive disorder(MDD), a mood disorder, is the impairment of excitatory synapses in the prefrontal cortex. Intriguingly, different types of treatment with fairly rapid antidepressant effects (within days or a few weeks), such as ketamine, electroconvulsive therapy and non-invasive neurostimulation, seem to converge on enhancement of neural plasticity. However, the forms and mechanisms of plasticity that link antidepressant interventions to the restoration of excitatory synaptic function are still unknown. In this Review, we highlight preclinical research from the past 15 years showing that ketamine and psychedelic drugs can trigger the growth of dendritic spines in cortical pyramidal neurons. We compare the longitudinal effects of various psychoactive drugs on neuronal rewiring, and we highlight rapid onset and sustained time course as notable characteristics for putative rapid-acting antidepressant drugs. Furthermore, we consider gaps in the current understanding of drug-evoked in vivo structural plasticity. We also discuss the prospects of using synaptic remodelling to understand other antidepressant interventions, such as repetitive transcranial magnetic stimulation. Finally, we conclude that structural neural plasticity can provide unique insights into the neurobiological actions of psychoactive drugs and antidepressant interventions.

Effects of antidepressant and antipsychotic medication on peripheral brain-derived neurotrophic factor concentration: Systematic review and meta-analysis

Brain-derived neurotrophic factor (BDNF) is an important regulatory protein in the pathophysiology of psychiatric disorders. Several studies have reported the relationship between peripheral BDNF concentrations and the use of psychoactive drugs. However, the results remain controversial. This study aimed to evaluate the effects of psychoactive drugs on BDNF concentrations and to explore the association between changes in BDNF concentrations and improvements in clinical scores. A systematic review and meta-analysis were conducted. Six electronic databases, including PubMed, Scopus, Medline, Web of Science, Google Scholar and Science Direct, were searched. Changes in BDNF concentrations were compared before and after psychoactive treatment, using the standardized mean difference (SMD) and 95 % confidence interval (95 % CI). Twenty-three studies were included. A significant increase in serum BDNF concentrations was observed after treatment with antipsychotics (SMD=0.43; 95 %CI: 0.26, 0.60) and antidepressants (SMD=0.49; 95 %CI: 0.23, 0.74). However, the plasma BDNF concentration was not affected by antidepressant and antipsychotic medication. Although an improvement in clinical scores was observed after treatment, no significant association was observed between changes in BDNF concentrations and the changes in the Positive and Negative Syndrome Scale (PANSS) and the Hamilton Depression Rating Scale (HAM-D) scores. In conclusion, antidepressants and antipsychotics increase serum BDNF concentrations.

Effects of acute and chronic methylphenidate on prepulse inhibition: A sex difference study in Wistar rats

BackgroundThe utilization of methylphenidate (MPH) is experiencing a notable surge within the adult population. This growth can be attributed to two key factors: its recreational and cognitive enhancement purposes, as well as the rising prevalence of ADHD diagnoses within this population. This study examined acute and chronic oral MPH effects on attention in male and female Wistar rats. To this end, we used a prepulse inhibition (PPI) task, which is widely used to assess psychoactive drug effects in both humans and rodents. This task allowed us to evaluate changes in attention by analyzing sensorimotor gating associated with stimulus selection process. MethodsAnimals were administered a clinically relevant dose of MPH (5 mg/kg) daily for seven days. The estrous cycle phases of the female rats were measured during behavioral sessions. The PPI task was conducted 20 min after drug administration on day 1 (acute), day 7 (chronic), and 48 h post-treatment. ResultsResults indicated that both acute and chronic MPH treatment impaired PPI expression in male rats, but not in female rats, regardless of their estrous cycle phase. Furthermore, a differential effect of chronic MPH treatment on the PPI task was found in male rats. Specifically, on the seventh treatment day, the PPI effect was observed when animals undertook the PPI task for the first time but was impaired in those animals in which the initial PPI session occurred under the acute influence of the drug (day 1). ConclusionsThese findings suggest that the impact of MPH on sensorimotor gating responses may vary based on sex and task experience, possibly leading to state-dependent effects in healthy individuals.

Insights into Psychoactive Drug Effects: The Role of Drug Discrimination Techniques

Psychoactive drugs exert profound effects on the central nervous system, influencing behavior and perception. Understanding these effects is crucial for both scientific research and clinical practice. This article provides an overview of the application of drug discrimination techniques in studying the subjective effects, pharmacological mechanisms, individual differences, and drug classification of psychoactive substances. Through drug discrimination models, researchers gain insights into the pharmacological specificity and predictive validity of these substances, particularly hallucinogens such as LSD and cannabinoids like THC. The article highlights the contributions of drug discrimination techniques in elucidating the pharmacological actions of psychoactive drugs, offering opportunities for further exploration into their therapeutic potential and abuse-related properties.

A reinforcement learning model with choice traces for a progressive ratio schedule.

The progressive ratio (PR) lever-press task serves as a benchmark for assessing goal-oriented motivation. However, a well-recognized limitation of the PR task is that only a single data point, known as the breakpoint, is obtained from an entire session as a barometer of motivation. Because the breakpoint is defined as the final ratio of responses achieved in a PR session, variations in choice behavior during the PR task cannot be captured. We addressed this limitation by constructing four reinforcement learning models: a simple Q-learning model, an asymmetric model with two learning rates, a perseverance model with choice traces, and a perseverance model without learning. These models incorporated three behavioral choices: reinforced and non-reinforced lever presses and void magazine nosepokes, because we noticed that male mice performed frequent magazine nosepokes during PR tasks. The best model was the perseverance model, which predicted a gradual reduction in amplitudes of reward prediction errors (RPEs) upon void magazine nosepokes. We confirmed the prediction experimentally with fiber photometry of extracellular dopamine (DA) dynamics in the ventral striatum of male mice using a fluorescent protein (genetically encoded GPCR activation-based DA sensor: GRABDA2m). We verified application of the model by acute intraperitoneal injection of low-dose methamphetamine (METH) before a PR task, which increased the frequency of magazine nosepokes during the PR session without changing the breakpoint. The perseverance model captured behavioral modulation as a result of increased initial action values, which are customarily set to zero and disregarded in reinforcement learning analysis. Our findings suggest that the perseverance model reveals the effects of psychoactive drugs on choice behaviors during PR tasks.

The Effect of Psychoactive Substances Used on Clinical Outcomes in Injured Drivers Referred to Emergency Medicine; Case-Control Study

Objective: The use of psychoactive substances increases the risk of accidents. This study evaluated the relationship between the type of psychoactive substances among traffic injured admitted to the medical center. Methods: Injured drivers (100 used drugs), (260 control group), who were transferred to 7-Tir Hospital from April 2021 to March 2022 were studied. The information related to the accident scene, personal characteristics, and the substance used was collected from the police and the medical center documents. We used multiple logistic regression to find the important factor in outcomes. Results: The mean age of the case group (37.49 ±13.61) compared to the control group (34.18 ±14.05) was significant (p=0.044). The most common substances in the case group were opioids which had the highest mean age (41.90 ± 13.541). Injured who used sedatives had higher signs of head trauma than the others. Also, being guilty had a remarkable difference in the groups (94.6 vs 62.4 p= <0.001). Motorcyclist drivers were 185(65%) as responsible for the accident, in addition, 69(69%) were in the case group. Head trauma, type of accident, and level of triage had a significant effect on the death of the injured. Conclusion: Using sedatives causes increased head trauma. Driving under the effect of psychoactive drugs is more common among motorcycle drivers, and a large percentage of them were guilty of accidents.

Context is a Critical for Psychoactive Drug Effects.

Context is a Critical for Psychoactive Drug Effects.

Anxiogenic doses of rapamycin prevent URB597-induced anti-stress effects in socially defeated mice

Repeated exposure to psychosocial stress modulates the endocannabinoid system, particularly anandamide (AEA) signaling in brain regions associated with emotional distress. The mTOR protein regulates various neuroplastic processes in the brain disrupted by stress, including adult hippocampal neurogenesis. This kinase has been implicated in multiple effects of cannabinoid drugs and the anti-stress behavioral effects of psychoactive drugs. Therefore, our hypothesis is that enhancing AEA signaling via pharmacological inhibition of the fatty acid amide hydrolase (FAAH) enzyme induces an anti-stress behavioral effect through an mTOR-dependent mechanism. To test this hypothesis, male C57Bl6 mice were exposed to social defeat stress (SDS) for 7 days and received daily treatment with either vehicle or different doses of the FAAH inhibitor, URB597 (0.1; 0.3; 1 mg/Kg), alone or combined with rapamycin. The results suggested that URB597 induced an inverted U-shaped dose–response curve in mice subjected to SDS (with the intermediate dose of 0.3 mg/kg being anxiolytic, and the higher tested dose of 1 mg/Kg being anxiogenic). In a second independent experiment, rapamycin treatment induced an anxiogenic-like response in control mice. However, in the presence of rapamycin, the anxiolytic dose of URB597 treatment failed to reduce stress-induced anxiety behaviors in mice. SDS exposure altered the hippocampal expression of the mTOR scaffold protein Raptor. Furthermore, the anxiogenic dose of URB597 decreased the absolute number of migrating doublecortin (DCX)-positive cells in the dentate gyrus, suggesting an anti-anxiety effect independent of newly generated/immature neurons. Therefore, our results indicate that in mice exposed to repeated psychosocial stress, URB597 fails to counteract the anxiogenic-like response induced by the pharmacological dampening of mTOR signaling.

Decoding effects of psychoactive drugs in a high-dimensional space of eye movements in monkeys.

Oculomotor behavior has been shown to be correlated with mental disorders in clinics, making it promising for disease diagnosis. Here we developed a thorough oculomotor test toolkit, involving saccade, smooth pursuit, and fixation, allowing the examination of multiple oculomotor parameters in monkey models induced by psychoactive drugs. Eye movements were recorded after daily injections of phencyclidine (PCP) (3.0mg/kg), ketamine (0.8mg/kg) or controlled saline in two macaque monkeys. Both drugs led to robust reduction in accuracy and increment in reaction time during high cognitive-demanding tasks. Saccades, smooth pursuit, and fixation stability were also significantly impaired. During fixation, the involuntary microsaccades exhibited increased amplitudes and were biased toward the lower visual field. Pupillary response was reduced during cognitive tasks. Both drugs also increased sensitivity to auditory cues as reflected in auditory evoked potentials (AEPs). Thus, our animal model induced by psychoactive drugs produced largely similar abnormalities to that in patients with schizophrenia. Importantly, a classifier based on dimension reduction and machine learning could reliably identify altered states induced by different drugs (PCP, ketamine and saline, accuracy=93%). The high performance of the classifier was reserved even when data from one monkey were used for training and testing the other subject (averaged classification accuracy=90%). Thus, despite heterogeneity in baseline oculomotor behavior between the two monkeys, our model allows data transferability across individuals, which could be beneficial for future evaluation of pharmaceutical or physical therapy validity.

The Use of Touchscreen-Based Methods to Characterize Effects of Psychoactive Drugs on Executive Function in Nonhuman Primates

The Use of Touchscreen-Based Methods to Characterize Effects of Psychoactive Drugs on Executive Function in Nonhuman Primates

Experimental Evidence on Age-related Differential Outcomes Associated With Substance Abuse.

Growing evidence indicates that adolescent substance abuse is now an alarming concern that imposes a considerable socio-economic burden on societies. On the other hand, numerous studies have shown that due to specific neurophysiological features, the brain is more vulnerable to the adverse effects of psychoactive drugs at an early age. Unfortunately, these negative effects are not limited to the period of drug use, but can persistently affect the brain's responsiveness to future exposures to the same or other types of drug. For researchers to develop pharmacological strategies for managing substance abuse disorders, they need to gain a deep understanding of the differences in behavioral outcomes associated with each type of drug across different age groups. The present study was conducted to review the experimental evidence revealing the mentioned differential effects with an emphasis on common drugs of abuse, including cocaine, nicotine, cannabis, and opioids. Although the cellular mechanisms underlying age-related effects have not been exclusively addressed for each drug, the most recent results are presented and discussed. Future studies are required to focus on these mechanisms and reveal how molecular changes during brain development can result in differential responses to drugs at the behavioral level.

Epigenetic Effects of Psychoactive Drugs.

Currently, and globally, we are facing the worst epidemic of psychoactive drug abuse resulting in hundreds of thousands of lives annually. Besides alcohol and opioid use and misuse, there has been an increase in illicit abuse of psychostimulants. Epigenetics is a relatively novel area of research that studies heritable alterations in gene expression. Long-term administration of psychoactive drugs may lead to transcriptional changes in brain regions related to drug-seeking behaviors and rewards that can be passed down transgenerationally. Epigenetic biomarkers such as DNA methylation and histone modifications contribute to disease diagnoses. This review aims to look at the epigenetic modifications brought forth by psychoactive drug abuse.

G protein-coupled receptor modulation of striatal dopamine transmission: Implications for psychoactive drug effects.

Dopamine transmission in the striatum is a critical mediator of the rewarding and reinforcing effects of commonly misused psychoactive drugs. G protein-coupled receptors (GPCRs) that bind a variety of neuromodulators including dopamine, endocannabinoids, acetylcholine and endogenous opioid peptides regulate dopamine release by acting on several components of dopaminergic circuitry. Striatal dopamine release can be driven by both somatic action potential firing and local mechanisms that depend on acetylcholine released from striatal cholinergic interneurons. GPCRs that primarily regulate somatic firing of dopamine neurons via direct effects or modulation of synaptic inputs are likely to affect distinct aspects of behaviour and psychoactive drug actions compared with those GPCRs that primarily regulate local acetylcholine-dependent dopamine release in striatal regions. This review will highlight mechanisms by which GPCRs modulate dopaminergic transmission and the relevance of these findings to psychoactive drug effects on physiology and behaviour.

Immunomodulatory properties of caffeine and caffeine-treated immune cells in depression-like state

Depression is one of the leading global health problems worldwide. A significant increase in prevalence among the working-age population, as well as high comorbidity, partial or complete drug resistance in a third of patients determines the need to develop new approaches to the treatment of depression. Violation of mutual regulation of the main homeostatic systems plays an important role in the pathogenesis of depression. Psycho- and immunopathology are closely interrelated: pathological changes in the functioning of both systems occur simultaneously and are interdependent. This determines the prospects for the treatment of depression based on immunological approaches. Caffeine, a drug known for its psychoneuromodulatory properties, is an adenosine receptor antagonist with a pronounced dose-dependent effect. Adenosine receptors are expressed by both CNS cells and cells of the immune system, which determines its immunomodulatory properties. The similarity of both phenotypes and functions of the cellular elements of the immune and nervous systems, as well as the unidirectional effect of most psychoactive drugs on the central nervous system and the immune system, determines the interest in studying the immunomodulatory properties of caffeine for a targeted effect on the functional activity of immune cells, with a view to their subsequent use as model objects for the normalization of neuroimmune regulatory connections disturbed in a depressive state. Previously, we first demonstrated the possibility of editing depression-like behavior by immune cells precultivated with caffeine and showed the central mechanisms of this effect aimed at stimulating neuroplasticity processes and reducing neuroinflammation. The aim of this study was to evaluate the functional phenotype of immune cells in depressive-like animals after in vitro treatment of cells with caffeine, as well as the effects of transplantation of caffeine-precultured immune cells on the parameters of the functional activity of the immune system of syngeneic depressive-like recipients. As a result of the study, it was shown that low concentrations of caffeine increase the spontaneous and mitogen-induced proliferative activity of splenocytes of depression-like male mice (CBA x C57BL/6)F1 in vitro; this changes the spontaneous and mitogen-stimulated production of cytokines TNFa IL-1b, IFNg, IL-2, and IL-10 by these cells. After intravenous administration of the precultured with caffeine depression-like donor’s splenocytes to syngeneic depression-like recipients, stimulation of the humoral immune response was observed in the latter, assessed by an increase in both the relative and absolute number of antibody-forming spleen cells. Stimulation of spontaneous proliferative activity of lymphocytes in splenocyte culture was also registered. The data obtained indicate a positive effect of caffeine in vitro on the immune cell’s functional activity, as well as a positive immunomodulatory effect of the immune cells precultured with caffeine in a depression-like state in vivo.

Effect of psychoactive substances on cardiac and locomotory activity of juvenile marbled crayfish Procambarus virginalis

Pharmaceutically active compounds are common and increasing in the aquatic environment. Evidence suggests they have adverse effects on non-target organisms, and they are classified as emerging pollutants for a variety of aquatic organisms. To determine the effects of environmentally relevant levels of psychoactive compounds on non-target organisms, we analyzed cardiac and locomotory activity in early developmental stages of marbled crayfish Procambarus virginalis. Responses to sertraline, methamphetamine, and a mixture of citalopram, oxazepam, sertraline, tramadol, venlafaxine, and methamphetamine at a concentration of 1 µg L-1 of each compound were assessed. On day four of exposure, cardiac activity was recorded for 5 min, and on day eight, locomotory activity was recorded for 15 min. There was a significant increase (p < 0.01) in heart rate in methamphetamine-exposed and Mix-exposed juveniles compared to the unexposed control and there was significant difference (p < 0.01) in proportion of time (activity %) was observed with sertraline-exposed, whereas velocity, and distance moved did not significantly differ (p > 0.05) in exposed and control animals. These findings revealed that low concentrations of chemicals and their mixtures can modify the physiological state of aquatic animals without outward manifestations (activity, distance moved, and velocity). Aquatic animals can be impacted earlier than is visible, but effects can potentially lead to substantial changes in populations and in ecosystem processes. Additional research to investigate chemical combinations, exposure systems, and organism physiological and molecular responses may provide evidence of broad impact of environmental pharmaceuticals.

A primer on sleeping, dreaming, and psychoactive agents

ABSTRACT As a necessary part of physiological and emotional well-being, sleep is often overlooked or undervalued in Western society, in spite of the role restorative sleep plays in growth, healing and recovery, immune response, and emotional regulation. The effect of psychoactive drugs on sleep, including pharmacological substances meant to assist in sleep, is notable and profound, especially in their disruption of REM sleep, the stage of sleep associated with dreaming. This article provides an overview of sleep stages, the brain and sleep, sleep disorders, and the effect of various psychoactive drugs on sleep architecture and hygiene. Future research that treats substance use and sleep as bi-directional in nature and longitudinally explores sleep-related interventions in treatment and longer-term recovery that are sustainable and person-centered is merited.

Deletion of Cryab increases the vulnerability of mice to the addiction-like effects of the cannabinoid JWH-018 via upregulation of striatal NF-κB expression.

Synthetic cannabinoids have exhibited unpredictable abuse liabilities, especially self-administration (SA) responses in normal rodent models, despite seemingly inducing addiction-like effects in humans. Thus, an efficient pre-clinical model must be developed to determine cannabinoid abuse potential in animals and describe the mechanism that may mediate cannabinoid sensitivity. The Cryab knockout (KO) mice were recently discovered to be potentially sensitive to the addictive effects of psychoactive drugs. Herein, we examined the responses of Cryab KO mice to JWH-018 using SA, conditioned place preference, and electroencephalography. Additionally, the effects of repeated JWH-018 exposure on endocannabinoid- and dopamine-related genes in various addiction-associated brain regions were examined, along with protein expressions involving neuroinflammation and synaptic plasticity. Cryab KO mice exhibited greater cannabinoid-induced SA responses and place preference, along with divergent gamma wave alterations, compared to wild-type (WT) mice, implying their higher sensitivity to cannabinoids. Endocannabinoid- or dopamine-related mRNA expressions and accumbal dopamine concentrations after repeated JWH-018 exposure were not significantly different between the WT and Cryab KO mice. Further analyses revealed that repeated JWH-018 administration led to possibly greater neuroinflammation in Cryab KO mice, which may arise from upregulated NF-κB, accompanied by higher expressions of synaptic plasticity markers, which might have contributed to the development of cannabinoid addiction-related behavior in Cryab KO mice. These findings signify that increased neuroinflammation via NF-κB may mediate the enhanced addiction-like responses of Cryab KO mice to cannabinoids. Altogether, Cryab KO mice may be a potential model for cannabinoid abuse susceptibility.

Effects of Psychoactive Substances on Some Biochemical Parameters and Histopathology of Kidney in Male Albino Rats

Effects of Psychoactive Substances on Some Biochemical Parameters and Histopathology of Kidney in Male Albino Rats

A primer on sleeping, dreaming, and psychoactive agents

ABSTRACT As a necessary part of physiological and emotional well-being, sleep is often overlooked or undervalued in Western society, in spite of the role restorative sleep plays in growth, healing, and recovery, immune response, and emotional regulation. The effect of psychoactive drugs on sleep, including pharmacological substances meant to assist in sleep, is notable and profound, especially in their disruption of REM sleep, the stage of sleep associated with dreaming. This article provides an overview of sleep stages, the brain and sleep, sleep disorders, and the effect of various psychoactive drugs on sleep architecture and hygiene. Future research, which treats substance use and sleep as bi-directional in nature and longitudinally explores sleep-related interventions in treatment and longer-term recovery that are sustainable and person-centered is merited.

Neurobiological mechanisms of psychosis in epilepsy: Findings from neuroimaging studies.

Despite the high prevalence and clinical importance of comorbid psychosis in epilepsy, its neurobiological mechanisms remain understudied. This narrative mini-review aims to provide an overview of recent updates in in vivo neuroimaging studies on psychosis in epilepsy, including structural and diffusion magnetic resonance imaging (MRI) and functional and molecular imaging, and to discuss future directions in this field. While the conventional morphological analysis of structural MRI has provided relatively inconsistent results, advanced methods, including brain network analysis, hippocampal subregion volumetry, and machine learning models, have recently provided novel findings. Diffusion MRI, for example, has revealed a reduction in white matter integrity mainly in the frontal and temporal lobes, as well as a disruption of brain white matter networks. Functional neuroimaging, such as perfusion single-photon emission computed tomography (SPECT) or fluorodeoxyglucose positron emission tomography (FDG-PET), often identifies hyperactivity in various brain regions. The current limitations of these more recent studies may include small and sometimes heterogeneous samples, insufficient control groups, the effects of psychoactive drugs, and the lack of longitudinal analysis. Further investigations are required to establish novel treatments and identify clinical diagnostic or disease-monitoring biomarkers in psychosis in epilepsy.