Repeated Cannabidiol treatment reduces cocaine intake and modulates neural proliferation and CB1R expression in the mouse hippocampus

Luján, Miguel Ángel; Castro‐Zavala, Adriana; Alegre-Zurano, Laia; Valverde, Olga

doi:10.1016/j.neuropharm.2018.09.043

Cited by 106 publications

(157 citation statements)

References 80 publications

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“…For this reason, comparisons with other previous works are limited. The closest approximate was reported in Luján et al (2018). In this previous study, we showed that animals treated with CBD (20 mg/kg) during the acquisition phase of cocaine operant taking extinguished seeking behavior in a similar extent than control mice.…”

Section: Discussionsupporting

confidence: 78%

“…The self-administration procedure here employed was conducted as previously described in Tourino et al (2012) and Luján et al (2018;2019). Surgical implantation of the catheter into the jugular vein was performed following anaesthetization with a mixture of Ketamine hydrochloride (100 mg/kg; Imalgène1000, Lyon, France) and…”

Section: Surgical Proceduresmentioning

confidence: 99%

“…However, available evidence supporting a 5 protective role of CBD in pre-clinical models of volitional drug seeking, and its mode of action, is still scarce. So far, two studies have suggested that CBD administration can reduce cocaine intake in mice (Luján et al, 2018) and rats . A single report by Gonzalez-Cuevas et al (2018) supported the treatment potential of CBD in reducing cue-and stress-induced retrieval of cocaine seeking behavior in rats.…”

Section: Introductionmentioning

confidence: 99%

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The effects of cannabidiol on cue- and stress-induced reinstatement of cocaine seeking behavior in mice are reverted by the CB1 receptor antagonist AM4113

Luján

Alegre-Zurano

Martín‐Sánchez

et al. 2020

Preprint

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Cocaine addiction is a brain disorder characterized by the consumption of the drug despite harmful consequences, the loss of control over drug intake and increased risk of relapse. Albeit prolonged research efforts, there is no available medication approved for the treatment of cocaine addiction. In the last decade, cannabinoid-based compounds have drawn increased interest for its potential therapeutic applications in various psychiatric conditions. Cannabidiol, a non-psychotomimetic constituent of the C. sativa plant, shows promising results in rodent models of anxiety, schizophrenia, depression and drug addiction. However, the specific effects and mechanisms of action of cannabidiol in a rodent model of extinction-based abstinence and drug seeking relapse remain unclear. Here, we administered cannabidiol (20 mg/kg) to male CD-1 mice trained to self-administer cocaine (0.75 mg/kg/inf) during extinction training (8-12 days). Then, we evaluated the reinstatement of cocaine seeking induced by cues, stress and drug priming. To ascertain the participation of CB1 receptors in these behavioral responses, we systemically administered the neutral cannabinoid antagonist AM4113 (5 mg/kg) before each reinstatement session. The results document that cannabidiol (20 mg/kg) does not modulate extinction training but attenuates 'extinction burst' responding after one cannabidiol injection. Furthermore, cannabidiol specifically blocked the reinstatement of cocaine seeking triggered by a cue presentation, an effect prevented by AM4113 (5 mg/kg). Unexpectedly, cannabidiol facilitated stress-induced reinstatement of cocaine seeking behavior, also by a CB1-dependent mechanism.Finally, cannabidiol did not affect cocaine-primed (10 mg/kg) precipitation of cocaine seeking. Our results reveal a series of complex changes induced by cannabidiol treatment with opposite implications for the reinstatement of cocaine seeking behavior that may limit therapeutic opportunities. The activity of CB1 receptors seems to play a 3 crucial role in the expression of cannabidiol-induced neuroplasticity underlying both the desirable and undesirable reinstatement effects here detailed.

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Section: Discussionsupporting

confidence: 78%

Section: Surgical Proceduresmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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The effects of cannabidiol on cue- and stress-induced reinstatement of cocaine seeking behavior in mice are reverted by the CB1 receptor antagonist AM4113

Luján

Alegre-Zurano

Martín‐Sánchez

et al. 2020

Preprint

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“…The same procedure was followed for cocaine‐induced CPP, but in this case, mice were not food deprived, as previously described (Luján, Castro‐Zavala, Alegre‐Zurano, & Valverde, ). The conditioning phase consisted of four pairings: Mice received an i.p.…”

Section: Methodsmentioning

confidence: 99%

“…The SA experiment was carried out in mouse operant chambers (Model ENV‐307A‐CT, Med Associates, Inc. Cibertec S.A.), as previously described with some minor modifications (López‐Arnau et al, ; Luján et al, ; Soria, Barbano, Maldonado, & Valverde, ). The chambers were housed in sound‐ and light‐attenuated boxes and contained two holes, one of which was defined as active and the other as inactive.…”

Section: Methodsmentioning

confidence: 99%

Prenatal and postnatal alcohol exposure increases vulnerability to cocaine addiction in adult mice

Cantacorps

Montagud‐Romero

Luján

et al. 2020

British J Pharmacology

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Background and Purpose Alcohol exposure in utero may lead to a wide range of long‐lasting morphological and behavioural deficiencies known as fetal alcohol spectrum disorders (FASD), associated with a higher risk of later developing neuropsychiatric disorders. However, little is known about the long‐term consequences of cocaine use and abuse in individuals with FASD. This study aimed to investigate the effects of maternal binge alcohol drinking during prenatal and postnatal periods on cocaine reward‐related behaviours in adult offspring. Experimental Approach Pregnant C57BL/6 female mice were exposed to an experimental protocol of binge alcohol consumption (drinking‐in‐the‐dark test) from gestation to weaning. Male offspring were subsequently left undisturbed until reaching adulthood and were tested for cocaine‐induced motivational responses (conditioned place preference, behavioural sensitization and operant self‐administration). Protein expression of dopamine‐ and glutamate‐related molecules was assessed following cocaine‐induced reinstatement. Key Results The results show that prenatal and postnatal alcohol exposure enhanced the preference for the cocaine‐paired chamber in the conditioned place preference test. Furthermore, early alcohol‐exposed mice displayed attenuated cocaine‐induced behavioural sensitization but also higher cocaine self‐administration. Furthermore, alterations in glutamatergic excitability (GluA1/GluA2 ratio) and ΔFosB expression were found in the prefrontal cortex and the striatum of alcohol‐exposed mice after cocaine‐primed reinstatement. Conclusion and Implications Our findings demonstrate that maternal binge‐like alcohol consumption during gestation and lactation alters sensitivity to the reinforcing effects of cocaine in adult offspring mice. Together, such data suggest that prenatal and postnatal alcohol exposure may underlie an enhanced susceptibility of alcohol‐exposed offspring to develop drug addiction later in adulthood.

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The interaction between cannabinoids and long‐term synaptic plasticity: A survey on memory formation and underlying mechanisms

Azarfarin,

Ghadiri,

Dadkhah

et al. 2024

Cell Biochemistry & Function

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Synaptic plasticity, including long‐term potentiation (LTP) and long‐term depression (LTD), is an essential phenomenon in memory formation as well as maintenance along with many other cognitive functions, such as those needed for coping with external stimuli. Synaptic plasticity consists of gradual changes in the biochemistry and morphology of pre‐ and postsynaptic neurons, particularly in the hippocampus. Consuming marijuana as a primary source of exocannabinoids immediately impairs attention and working memory‐related tasks. Evidence regarding the effects of cannabinoids on LTP and memory is contradictory. While cannabinoids can affect a variety of specific cannabinoid receptors (CBRs) and nonspecific receptors throughout the body and brain, they exert miscellaneous systemic and local cerebral effects. Given the increasing use of cannabis, mainly among the young population, plus its potential adverse long‐term effects on learning and memory processes, it could be a future global health challenge. Indeed, the impact of cannabinoids on memory is multifactorial and depends on the dosage, timing, formula, and route of consumption, plus the background complex interaction of the endocannabinoids system with other cerebral networks. Herein, we review how exogenously administrated organic cannabinoids, CBRs agonists or antagonists, and endocannabinoids can affect LTP and synaptic plasticity through various receptors in interaction with other cerebral pathways and primary neurotransmitters.

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Repeated Cannabidiol treatment reduces cocaine intake and modulates neural proliferation and CB1R expression in the mouse hippocampus

Cited by 106 publications

References 80 publications

The effects of cannabidiol on cue- and stress-induced reinstatement of cocaine seeking behavior in mice are reverted by the CB1 receptor antagonist AM4113

The effects of cannabidiol on cue- and stress-induced reinstatement of cocaine seeking behavior in mice are reverted by the CB1 receptor antagonist AM4113

Prenatal and postnatal alcohol exposure increases vulnerability to cocaine addiction in adult mice

The interaction between cannabinoids and long‐term synaptic plasticity: A survey on memory formation and underlying mechanisms

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