The 5-HT6R agonist E-6837 and the antagonist SB-271046 reverse the psychotic-like behaviors induced by ketamine
Schizophrenia is a serious mental disorder that affects 1% of the world’s population. Although various therapeutic tools have been developed since the appearance of the first generation of antipsychotics, the effect of these agents does not manage to attenuate a significant part of psychotic symptoms. Ketamine is an anesthetic agent able to produce psychotic-like symptoms through the antagonism of the glutamatergic N-methyl-d-aspartic acid (NMDA) receptors (NMDARs). This drug has been widely used to study new pharmacological tools with potential antipsychotic properties. On the contrary, it is known that the 5-HT6 recept...
Source: Behavioural Pharmacology - June 1, 2022 Category: Drugs & Pharmacology Tags: Short Report Source Type: research
Biphasic reward effects are characteristic of both lorcaserin and drugs of abuse: implications for treatment of substance use disorders
In conclusion, drugs of abuse and related compounds often act as biphasic modifiers of reward behavior, especially when evaluated over a broad range of doses. This property may reflect the underlying physiology of the reward system, allowing homeostatic influences on behavior. (Source: Behavioural Pharmacology)
Source: Behavioural Pharmacology - June 1, 2022 Category: Drugs & Pharmacology Tags: Review Articles Source Type: research
Cholinergic models of memory impairment in animals and man: scopolamine vs. biperiden
Scopolamine has been used as a pharmacologic model for cognitive impairments in dementia and Alzheimer’s disease. The validity of this model seems to be limited because findings in animals do not readily translate to novel treatments in humans. Biperiden is also a cholinergic deficit model for cognitive impairments but specifically blocks muscarinic M1 receptors. The effects of scopolamine and biperiden (and pirenzepine) are compared in animal studies and related to findings in humans. It is concluded that the effects on cognitive functions are different for scopolamine and biperiden, and they should be considered as dif...
Source: Behavioural Pharmacology - June 1, 2022 Category: Drugs & Pharmacology Tags: Review Articles Source Type: research
The interactive effects of verapamil and CB1 cannabinoid receptor antagonist/inverse agonist, AM251 on passive avoidance learning and memory in rat
In this study, we examined the effects of an acute administration of the cannabinoid CB1 receptors antagonist/inverse agonist AM251 following a chronic administration of the Ca2+ channel blocker verapamil on PAL. Male Wistar rats were administered verapamil (10, 25 and 50 mg/kg) or saline intraperitoneally (i.p) daily for 13 days (n = 10/group). After this treatment period, a learning test (acquisition) was performed, and a retrieval test was performed the following day. The results indicated that chronic systemic administration of verapamil (in a dose-dependent manner) impaired memory acquisition and retrieval. Pre-...
Source: Behavioural Pharmacology - March 20, 2022 Category: Drugs & Pharmacology Tags: Research Reports Source Type: research
Anti-aversive effect of 2-arachidonoylglycerol in the dorsolateral periaqueductal gray of male rats in contextual fear conditioning and Vogel tests
In conclusion, we confirmed the anti-aversive properties of 2-AG in the dlPAG through CB1 and CB2 mechanisms. However, these effects could vary according to the type of stressor and the anxiety model employed. (Source: Behavioural Pharmacology)
Source: Behavioural Pharmacology - March 20, 2022 Category: Drugs & Pharmacology Tags: Research Reports Source Type: research
Effects of cannabidiol and Δ9-tetrahydrocannabinol in the elevated plus maze in mice
The present study tested the effects of cannabidiol (CBD) alone, Δ-9-tetrahydrocannabinol (THC) alone, and CBD and THC in combination (15:1 ratio) in the elevated plus maze (EPM), a test useful for the study of anxiety. In dose-response studies, adult, male CD1 mice were injected intraperitoneally with (1) CBD alone (0–96 mg/kg), (2) THC alone (0–6.4 mg/kg) or (3) CBD+THC in a 15:1 combination (0.0 + 0.0 mg/kg to 96.0 + 6.4 mg/kg). Diazepam (2.5 mg/kg) was also tested as a positive control. It was found that diazepam significantly increased open arm time in the EPM. CBD alone had no significant effect at any d...
Source: Behavioural Pharmacology - March 20, 2022 Category: Drugs & Pharmacology Tags: Research Reports Source Type: research
Altered sleep during spontaneous cannabinoid withdrawal in male mice
We report that AM2389 produces decreases in locomotor activity that wane with repeated treatment, whereas discontinuation produces rebound increases in activity that persist for several days. Likewise, AM2389 initially produces profound increases in slow-wave sleep (SWS) and decreases in rapid eye movement (REM) sleep, as well as consolidation of sleep. By the third AM2389 treatment, this pattern transitions to decreases in SWS and total time sleeping. This pattern persists following AM2389 discontinuation and is accompanied by emergence of sleep fragmentation. Double-labeling immunohistochemistry for hypocretin/orexin (a ...
Source: Behavioural Pharmacology - March 20, 2022 Category: Drugs & Pharmacology Tags: Research Reports Source Type: research
Evidence for spontaneous cannabinoid withdrawal in mice
Although the behavioral effects of acute and chronic exposure to cannabinoids have been extensively studied in mice, spontaneous withdrawal following exposure to cannabinoids has not been well characterized in this species. To address this issue, different groups of mice were treated for 5 days with saline, 20–36 mg/kg/day of the CB partial agonist Δ9-tetrahydrocannabinol (Δ9-THC), or 0.06–0.1 mg/kg/day of the CB high-efficacy agonist AM2389. Initial studies assessed changes in observable behavior (paw tremors) that were scored from the recordings taken at 4 or 24 h after the last injection. Subsequently, radioteleme...
Source: Behavioural Pharmacology - March 20, 2022 Category: Drugs & Pharmacology Tags: Research Reports Source Type: research
Behavioral pharmacology of five novel synthetic cannabinoids
Newly emerging synthetic cannabinoid compounds continue to be found in the designer drug market. They are often targeted as a ‘legal high’ alternative to traditional cannabinoids via ‘darknet’ markets and their increased potency and efficacy are becoming a growing concern internationally. The purpose of this study was to determine whether 4-CN-CUMYL-BUTINACA, 4F-MDMB-BINACA, 5F-AEB, 5F-CUMYL-P7AICA and EMB-FUBINACA exhibited similar behavioral effects as Δ9-tetrahydrocannabinol (Δ9-THC). Locomotor activity was assessed in an open-field assay using Swiss-Webster mice. Male Sprague-Dawley rats were trained to discr...
Source: Behavioural Pharmacology - March 20, 2022 Category: Drugs & Pharmacology Tags: Research Reports Source Type: research
Blockage of ventrolateral periaqueductal gray matter cannabinoid 1 receptor increases dental pulp pain and pain-related subsequent learning and memory deficits in rats
This study aims at investigating the role of CB1R in the ventrolateral periaqueductal gray matter (vlPAG) on both pulpal pain and pain-related subsequent changes in learning and memory performances in rats. The adult male Wistar rats were cannulated in the vlPAG. The rats were pretreated by intra-vlPAG administration of selective CB1R antagonist AM-251 (2, 4 and 8 µg/rat) and vehicle dimethylsulfoxide. The drugs were microinjected 20 min before the induction of capsaicin-induced pulpalgia. The nociceptive behaviors were recorded for 40 min. Then, passive avoidance and spatial learning and memory were assessed using ...
Source: Behavioural Pharmacology - March 20, 2022 Category: Drugs & Pharmacology Tags: Research Reports Source Type: research
Spinal cannabinoid CB1 or CB2 receptors activation attenuates mechanical allodynia in streptozotocin-induced diabetic rats
Diabetes is a chronic disease associated with a high number of complications such as peripheral neuropathy, which causes sensorial disturbances and may lead to the development of diabetic neuropathic pain (DNP). The current treatment for DNP is just palliative and the drugs may cause severe adverse effects, leading to discontinuation of treatment. Thus, new therapeutic targets need to be urgently investigated. Studies have shown that cannabinoids have promising effects in the treatment of several pathological conditions, including chronic pain. Thus, we aimed to investigate the acute effect of the intrathecal injection of ...
Source: Behavioural Pharmacology - March 20, 2022 Category: Drugs & Pharmacology Tags: Short Report Source Type: research
Antinociceptive effects of minor cannabinoids, terpenes and flavonoids in Cannabis
Cannabis has been used for centuries for its medicinal properties. Given the dangerous and unpleasant side effects of existing analgesics, the chemical constituents of Cannabis have garnered significant interest for their antinociceptive, anti-inflammatory and neuroprotective effects. To date, Δ9-tetrahydrocannabinol (THC) and cannabidiol (CBD) remain the two most widely studied constituents of Cannabis in animals. These studies have led to formulations of THC and CBD for human use; however, chronic pain patients also use different strains of Cannabis (sativa, indica and ruderalis) to alleviate their pain. These strains c...
Source: Behavioural Pharmacology - March 20, 2022 Category: Drugs & Pharmacology Tags: Review Articles Source Type: research
Cannabinoid drugs against chemotherapy-induced adverse effects: focus on nausea/vomiting, peripheral neuropathy and chemofog in animal models
Although new drugs are being developed for cancer treatment, classical chemotherapeutic agents are still front-line therapies, despite their frequent association with severe side effects that can hamper their use. Cannabinoids may prevent or palliate some of these side effects. The aim of the present study is to review the basic research which has been conducted evaluating the effects of cannabinoid drugs in the treatment of three important side effects induced by classical chemotherapeutic agents: nausea and vomiting, neuropathic pain and cognitive impairment. Several published studies have demonstrated that cannabinoids ...
Source: Behavioural Pharmacology - March 20, 2022 Category: Drugs & Pharmacology Tags: Review Articles Source Type: research
The endocannabinoid system and drug-associated contextual memories
Drug abuse and addiction can be initiated and reinstated by contextual stimuli previously paired with the drug use. The influence exerted by the context on drug-seeking behaviour can be modelled in experimental animals with place-conditioning protocols. Here, we review the effects of cannabinoids in place conditioning and the therapeutic potential of the endocannabinoid system for interfering with drug-related memories. The phytocannabinoid Δ9-tetrahydrocannabinol (THC) tends to induce conditioned place preference (CPP) at low doses and conditioned place aversion at high doses; cannabidiol is devoid of any effect, yet it ...
Source: Behavioural Pharmacology - March 20, 2022 Category: Drugs & Pharmacology Tags: Review Articles Source Type: research
Translational models of cannabinoid vapor exposure in laboratory animals
Cannabis is one of the most frequently used psychoactive substances in the world. The most common route of administration for cannabis and cannabinoid constituents such as Δ-9-tetrahydrocannabinol (THC) and cannabidiol (CBD) is via smoking or vapor inhalation. Preclinical vapor models have been developed, although the vaporization devices and delivery methods vary widely across laboratories. This review examines the emerging field of preclinical vapor models with a focus on cannabinoid exposure in order to (1) summarize vapor exposure parameters and other methodological details across studies; (2) discuss the pharmacologi...
Source: Behavioural Pharmacology - March 20, 2022 Category: Drugs & Pharmacology Tags: Review Articles Source Type: research
