IBRO Neuroscience ReportsOctober 1, 2023Iker Bengoetxea de Tena, Jonatan Martínez‐Gardeazabal, Lorena Galera-López et al.
The mechanisms for encoding, storing and retrieving memories are abundant and complex. Among them, the protein kinase C (PKC) family of enzymes, and more specifically PKCɣ isoform, regulates important aspects of synaptic plasticity and memory. In addition, PKCɣ has been found to interact with cannabinoid receptors. In this study, we investigated the density and activity of cannabinoid receptors...
Cannabis use disorder (CUD) is widespread, and there is no pharmacotherapy to facilitate its treatment. AEF0117, the first of a new pharmacological class, is a signaling-specific inhibitor of the cannabinoid receptor 1 (CB1-SSi). AEF0117 selectively inhibits a subset of intracellular effects resulting from Δ9-tetrahydrocannabinol (THC) binding without modifying behavior per se. In mice and...
NeuropharmacologyJanuary 2019Rocio Saravia, Marc Ten-Blanco, Marina Julià-Hernández et al.
Δ9-tetrahydrocannabinol (THC) consumption during adolescence is reported to be a risk factor for the appearance of psychiatric disorders later in life. The interaction between genetic or environmental events and cannabinoid exposure in the adolescent period can also contribute to exacerbate behavioural deficits in adulthood. Here we investigate the effects of THC treatment as well as the...
Cannabis is the most consumed illicit drug worldwide. Its principal psychoactive component, Δ9-tetrahydrocannabinol (THC), affects multiple brain functions, including cognitive performance, by modulating cannabinoid type-1 (CB1) receptors. These receptors are strongly enriched in presynaptic terminals, where they modulate neurotransmitter release. We analyzed, through a proteomic screening of...
Activation of cannabinoid CB1 receptors (CB1R) by delta9-tetrahydrocannabinol (THC) produces a variety of negative effects with major consequences in cannabis users that constitute important drawbacks for the use of cannabinoids as therapeutic agents. For this reason, there is a tremendous medical interest in harnessing the beneficial effects of THC. Behavioral studies carried out in mice...
Social behavior plays a fundamental role in life of many animal species, allowing the interaction between individuals and sharing of experiences, needs, and goals across them. In humans, some neuropsychiatric diseases, including anxiety, posttraumatic stress disorder and autism spectrum disorders, are often characterized by impaired sociability. Here we report that...
Ecstasy is a drug that is usually consumed by young people at the weekends and frequently, in combination with cannabis. In the present study we have investigated the long-term effects of administering increasing doses of delta-9-tetrahydrocannabinol [THC; 2.5, 5, 10 mg/kg; i.p.] from postnatal day (pnd) 28 to 45, alone and/or in conjunction with 3,4-methylenedioxymethamphetamine [MDMA; two...
The potential therapeutic benefits of cannabinoid compounds have raised interest in understanding the molecular mechanisms that underlie cannabinoid-mediated effects. We previously showed that the acute amnesic-like effects of delta9-tetrahydrocannabinol (THC) were prevented by the subchronic inhibition of the mammalian target of rapamycin (mTOR) pathway. In the present study, we assess the...
Exogenous cannabinoids, such as delta9-tetrahydrocannabinol (THC), as well as the modulation of endogenous cannabinoids, affect cognitive function through the activation of cannabinoid receptors. Indeed, these compounds modulate a number of signalling pathways critically implicated in the deleterious effect of cannabinoids on learning and memory. Thus, the involvement of the mammalian target of...
ABSTRACT Repeated administration of 3,4‐methylenedioxymethamphetamine (MDMA) produces dopaminergic neurotoxicity in mice. However, it is still not clear whether this exposure induces deficits in cognitive processing related to specific subsets of executive functioning. We evaluated the effects of neurotoxic and non‐neurotoxic doses of MDMA (0, 3 and 30 mg/kg, twice daily for 4 days) on working...
The behavioral and neurochemical adaptations related to chronic 3,4-methylenedioxymethamphetamine (MDMA) treatment are largely unknown. In this study, we assessed whether repeated administration of MDMA would induce (a) context-dependent locomotor sensitization in mice and (b) changes in serotonin 5-HT(2A) and dopamine D₂ receptor functionality as measured by [³⁵S]GTPγS binding. Mice were...
The serotonergic system appears crucial for (±)-3,4-methylenedioxymethamphetamine (MDMA) reinforcing properties. Current evidence indicates that serotonin 5-HT2A receptors (5-HT2ARs) modulate mesolimbic dopamine (DA) activity and several behavioural responses related to the addictive properties of psychostimulants. This study evaluated the role of 5-HT2ARs in MDMA-induced reinforcement and...
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,...
There is evidence demonstrating changes in dopamine (DA) transmission in the nucleus accumbens (NAc) related to contingent versus non-contingent drug administration. The aim of this study was to evaluate basal and 3,4-methylenedioxymethamphetamine (MDMA)-stimulated DA levels in the NAc of mice that had previously received contingent and non-contingent infusions of MDMA. Contingent mice were...
MDMA effects are mediated by monoaminergic systems, which seem to play a central role in cocaine craving and relapse. CD1 mice trained to self-administer cocaine (1 mg/kg/infusion) underwent an extinction procedure in which the cues contingent with drug self-administration remained present. Mice achieving extinction were injected with MDMA (10 mg/kg), d-amphetamine (1 and 2 mg/kg) or saline and...
3,4-Methylenedioxymethamphetamine (MDMA) is a popular recreational drug widely abused by young people. The endocannabinoid system is involved in the addictive processes induced by different drugs of abuse. However, the role of this system in the pharmacological effects of MDMA has not yet been clarified. Locomotion, body temperature, and anxiogenic-like responses were evaluated after acute MDMA...
Several studies have suggested the existence of cognitive deficits after repeated or high doses of 3,4-methylenedioxymethamphetamine (MDMA) in humans and experimental animals. However, the extent of the impairments observed in learning or memory tasks remains unclear. The objective of this study was to evaluate the effects of different dosing regimens of MDMA on the ability of mice to learn and...
3, 4-Methylenedioxymethamphetamine (MDMA) and cannabis are widely abused illicit drugs that are frequently consumed in combination. Interactions between these two drugs have been reported in several pharmacological responses observed in animals, such as body temperature, anxiety, cognition, and reward. However, the interaction between MDMA and cannabis in addictive processes such as physical...
NeuropharmacologyJune 2006Evelyne Célérier, Therese Ahdepil, Helena Wikander et al.
The identification of the possible factors that might enhance the risk of developing drug addiction and related motivational disorders is crucial to reduce the prevalence of these problems. Here, we examined in mice whether the exposure to the anabolic-androgenic steroid nandrolone would affect the pharmacological and motivational effects induced by Delta(9)-tetrahydrocannabinol (THC), the...
A2A adenosine and CB1 cannabinoid receptors are highly expressed in the central nervous system, where they modulate numerous physiological processes including adaptive responses to drugs of abuse. Both purinergic and cannabinoid systems interact with dopamine neurotransmission (through A2A and CB1 receptors, respectively). Changes in dopamine neurotransmission play an important role in...
Abstract The involvement of µ‐opioid receptors in the rewarding properties of MDMA was explored in µ‐opioid receptor knockout mice using the conditioning place preference paradigm. The associated release of dopamine in the nucleus accumbens was investigated by in vivo microdialysis. A significant rewarding effect of MDMA (10 mg/kg, i.p.) was observed in both wild‐type and µ‐opioid receptor...
The involvement of dynorphin on Delta-9-tetrahydrocannabinol (THC) and morphine responses has been investigated by using mice with a targeted inactivation of the prodynorphin (Pdyn) gene. Dynorphin-deficient mice show specific changes in the behavioral effects of THC, including a reduction of spinal THC analgesia and the absence of THC-induced conditioned place aversion. In contrast, acute and...