Cannabinoids reward sensitivity in a neurodevelopmental animal model of schizophrenia: A brain stimulation reward study

Gallo, Alexandra; Bouchard, Claude; Fortier, Emmanuel; Ducrot, Charles; Rompré, Pierre‐Paul

doi:10.1016/j.euroneuro.2014.07.003

Cited by 11 publications

(11 citation statements)

References 49 publications

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“…A large body of literature has consistently linked cannabis use to the exacerbation of positive symptoms of schizophrenia. So far, very few studies have investigated whether THC exacerbates schizophrenia-like symptoms in adult animals [59][60][61][62][63][64]. Our study shows that THC can produce a broad range of deficits in healthy animals that resembled those observed in animal models of schizophrenia.…”

Section: Discussionmentioning

confidence: 53%

“…After excluding confounding effects on motor activity (see Material and Method), we found that THC administration at the lowest (0.1 mg/kg), but not the highest (1 mg/kg; a dose that did not produce place preference in Braida's study [58]), dose had beneficial effects on various correlates of schizophrenia (see above). While there is a large literature on THC exposure in adolescent rodents, few studies [59][60][61][62][63][64] have assessed THC effects on schizophrenia-related behavioral deficits in adult rodents. For instance, Malone et al, [62] reported that the prepulse inhibition deficit (an operational measure of sensorimotor gating) observed in adult rats reared in isolation was worsened by THC (1 and 3 mg/kg, i.v.).…”

Section: Discussionmentioning

confidence: 99%

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Differential effects of Δ9-tetrahydrocannabinol dosing on correlates of schizophrenia in the sub-chronic PCP rat model

2020

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Social withdrawal in the sub-chronic phencyclidine (PCP) rat model, a behavioral correlate of the negative symptoms of schizophrenia, results from deficits in brain endocannabinoid transmission. As cannabis intake has been shown to affect negatively the course and expression of psychosis, we tested whether the beneficial effects of endocannabinoid-mediated CB 1 activation on social withdrawal in PCP-treated rats (5 mg/kg, twice daily for 7 days)also occurred after administration of Δ9-tetrahydrocannabinol (THC; 0.1, 0.3, 1.0 mg/ kg, i.p.). In addition, we assessed whether THC affected two correlates of positive symptoms: 1) motor activity induced by d-amphetamine (0.5 mg/kg, i.p.), and 2) dopamine neuron population activity in the ventral tegmental area (VTA). After the motor activity test, the brains from d-amphetamine-treated animals were collected and processed for measurements of endocannabinoids and activation of Akt/GSK3β, two molecular markers involved in the pathophysiology of schizophrenia. In control rats, THC dose-dependently produced social interaction deficits and aberrant VTA dopamine neuron population activity similar to those observed in PCP-treated animals. In PCP-treated rats, only the lowest dose of THC reversed PCP-induced deficits, as well as PCP-induced elevation of the endocannabinoid anandamide (AEA) in the nucleus accumbens. Last, THC activated the Akt/GSK3β pathway dose-dependently in both control and PCP-treated animals. Taken together, these data suggest that only low doses of THC have beneficial effects on behavioral, neurochemical and electrophysiological correlates of schizophrenia symptoms. This observation may shed some light on the controversial hypothesis of marijuana use as self-medication in schizophrenic patients.

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Section: Discussionmentioning

confidence: 53%

Section: Discussionmentioning

confidence: 99%

Differential effects of Δ9-tetrahydrocannabinol dosing on correlates of schizophrenia in the sub-chronic PCP rat model

2020

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“…In a brain stimulation paradigm in young adult rats, reward thresholds following acute amphetamine are similarly elevated in NVHL and sham controls, yet this elevation drops off more rapidly in NVHL rats, indicating increased tolerance for amphetamine [69]. In a drug self-administration paradigm, NVHL rats show higher motivation for methamphetamine selfadministration under a progressive ratio schedule, but no differences in responding under a fixed ratio schedule of reinforcement [70].…”

Section: Psychostimulants: Amphetamine and Methamphetaminementioning

confidence: 90%

“…In addition, young adult but not adolescent NVHL rats exhibit a greater aversion to WIN in a conditioned place preference paradigm compared to controls, yet the opposite effect occurs for CB 1 receptor agonist ∆ 9 -tetrahydrocannabinnol (THC), where sham controls demonstrate an aversion for THC, which is not present in NVHL rats [85]. These findings are mirrored in a brain stimulation reward paradigm, where THC produces a weak attenuation of reward in sham controls, but not NVHL rats, and WIN has the opposite effect, attenuating reward in NVHL rats but enhancing it in controls [69]. The different effects of THC and WIN may be due to different pharmacokinetics between the two drugs (e.g.…”

Section: Ethanolmentioning

confidence: 99%

Schizophrenia and drug addiction comorbidity: recent advances in our understanding of behavioural susceptibility and neural mechanisms

Menne

Chesworth

2020

Neuroanatomy and Behaviour

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Schizophrenia is a severe psychiatric disorder which is worsened substantially by substance abuse/addiction. Substance abuse affects nearly 50% of individuals with schizophrenia, extends across several drug classes (e.g. nicotine, cannabinoids, ethanol, psychostimulants) and worsens overall functioning of patients. Prominent theories explaining schizophrenia and addiction comorbidity include the primary addiction hypothesis (i.e. schizophrenia susceptibility primes drug reward circuits, increasing drug addiction risk following drug exposure), the two-hit hypothesis (i.e. drug abuse and other genetic and/or environmental risk factors contribute to schizophrenia development) and the self-medication hypothesis (i.e. drug use alleviates schizophrenia symptoms). Animal models can be used to evaluate the utility and validity of these theories. Since this literature was last reviewed by Ng and colleagues in 2013 [Neurosci Biobehav Rev, 37(5)], significant advances have been made to our understanding of schizophrenia and substance abuse comorbidity. Here we review advances in the field since 2013, focussing on two key questions: 1) Does schizophrenia susceptibility increase susceptibility to drug addiction (assessing the primary addiction hypothesis), and 2) Do abused drugs exacerbate or ameliorate schizophrenia symptoms (assessing the two-hit hypothesis and the self-medication hypothesis). We addressed these questions using data from several schizophrenia preclinical models (e.g. genetic, lesion, neurodevelopmental, pharmacological) across drug classes (e.g. nicotine, cannabinoids, ethanol, psychostimulants). We conclude that addiction-like behaviour is present in several preclinical schizophrenia models, and drugs of abuse can exacerbate but also ameliorate schizophrenia-relevant behaviours. These behavioural changes are associated with altered receptor system function (e.g. dopaminergic, glutamatergic, GABAergic) critically implicated in schizophrenia and addiction pathology.

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“…Nonetheless, contrasting results have often been reported, even from the same authors. For example, a lack of effect of THC and other cannabinoid agonists has been reported (Arnold et al 2001a; Gallo et al 2014; Vlachou et al 2003), as well as decreases in the effectiveness of brain stimulation (Fokos and Panagis 2010; Katsidoni et al 2013; Mavrikaki et al 2010; Vlachou et al 2005; 2006; Vlachou et al 2007; Wiebelhaus et al 2015), an effect that was shown to be reversed by administration of very low doses, in the µg/kg range, of CB1 receptor antagonists (Vlachou et al 2003; 2005; Vlachou et al 2007). …”

Section: Intra-cranial Self-stimulationmentioning

confidence: 99%

Preclinical studies on the reinforcing effects of cannabinoids. A tribute to the scientific research of Dr. Steve Goldberg

Tanda

2016

Psychopharmacology

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Rationale The reinforcing effects of most abused drugs have been consistently demonstrated and studied in animal models, although those of marijuana were not, until the demonstration fifteen years ago that THC could serve as a reinforcer in self-administration (SA) procedures in squirrel monkeys. Until then, those effects were inferred using indirect assessments. Objectives The aim of this manuscript is to review the primary preclinical procedures used to indirectly and directly infer reinforcing effects of cannabinoid drugs. Methods Results will be reviewed from studies of cannabinoid-discrimination, intracranial-self-stimulation (ICSS), conditioned place preference (CPP), as well as change in levels of dopamine assessed in brain areas related to reinforcement, and finally from self-administration procedures. For each procedure, an evaluation will be made of the predictive validity in detecting the potential abuse liability of cannabinoids based on seminal papers, with the addition of selected reports from more recent years especially those from Dr. Goldberg’s research group. Results and Conclusions ICSS and CPP do not provide consistent results for the assessment of potential for abuse of cannabinoids. However, drug-discrimination and neurochemistry procedures appear to detect potential for abuse of cannabinoids, as well as several novel “designer cannabinoid drugs.” Though after 15 years it remains somewhat problematic transfer the self-administration model of marijuana abuse from squirrel monkeys to other species, studies with the former species have substantially advanced the field, and several reports have been published with consistent self-administration of cannabinoid agonists in rodents.

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Cannabinoids reward sensitivity in a neurodevelopmental animal model of schizophrenia: A brain stimulation reward study

Cited by 11 publications

References 49 publications

Differential effects of Δ9-tetrahydrocannabinol dosing on correlates of schizophrenia in the sub-chronic PCP rat model

Differential effects of Δ9-tetrahydrocannabinol dosing on correlates of schizophrenia in the sub-chronic PCP rat model

Schizophrenia and drug addiction comorbidity: recent advances in our understanding of behavioural susceptibility and neural mechanisms

Preclinical studies on the reinforcing effects of cannabinoids. A tribute to the scientific research of Dr. Steve Goldberg

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