Topiramate increases the rewarding properties of cocaine in young-adult mice limiting its clinical usefulness

Arenas, M. Carmen; Mateos-García, Ana; Manzanedo, Carmen; Rodrı́guez-Arias, Marta; Aguilar, M.A.; Navarrete, Francisco; Gutiérrez, María Salud García; Manzanares, Jorge; Miñarro, José

doi:10.1007/s00213-016-4409-4

Cited by 6 publications

(6 citation statements)

References 38 publications

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“…In the present study, priming-induced reinstatement of CPP was accompanied by an increase in the gene expression of DAT in the VTA. In contrast, we observed in a previous study that daily injection with cocaine during four sessions of place conditioning reduced VTA DAT gene expression (Arenas et al, 2016). Similar results have been reported by Siciliano et al (2016), who observed that cocaine self-administration modified the effects of cocaine on DAT, where this drug was less effective to inhibit dopamine uptake; although abstinence apparently normalized the dopamine system, DAT remained in a ‘primed’ state and the re-exposure to a single dose of cocaine reinstated the neural plasticity induced by this drug.…”

Section: Discussioncontrasting

confidence: 81%

“…Reinstatement tests were the same as those for Pre-C and Post-C (free ambulation for 15 min), except that the animals were tested 15 min after administering the corresponding experimental manipulation. We always employed this 15-min time lag in treatment due to the time needed to achieve the maximal effect of cocaine (Arenas et al, 2016; Maldonado et al, 2006; Titomanlio et al, 2013). Priming injections or social defeat took place in the vivarium, which constituted a non-contingent place to that of the previous conditioning procedure.…”

Section: Methodsmentioning

confidence: 99%

“…On the following day, after the confirmation of extinction of CPP, each group of mice received one of the following treatments before the reinstatement test (see Table 1): one group received an injection of vehicle plus an injection of saline (group Veh+Sal), two groups received an injection of 30 mg/kg or 60 mg/kg of CBD plus saline (CBD30+Sal and CBD60+Sal) and three groups received a priming injection with 5 mg/kg of cocaine plus vehicle or CBD (Veh+Coc, CBD30+Coc and CBD60+Coc). Half of the dose of cocaine administered during conditioning is effective as priming to induce reinstatement, as previously described for this paradigm (Arenas et al, 2016; Maldonado et al, 2006). First, mice received Veh or CBD and after an interval of 60 min they received Sal or Coc.…”

Section: Methodsmentioning

confidence: 99%

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Cannabidiol prevents priming- and stress-induced reinstatement of the conditioned place preference induced by cocaine in mice

et al. 2021

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Background: Cocaine dependence is an important problem without any effective pharmacological treatment. Some preclinical studies have suggested that cannabidiol (CBD), a component of the Cannabis sativa plant, could be useful for the treatment of cocaine use disorders. Aims: This work aims to evaluate the ability of CBD to reduce priming- and stress-induced reinstatement of the conditioned place preference (CPP) induced by cocaine. Methods: Young adult CD-1 male mice were allocated to 10 groups ( n = 12/group), conditioned with cocaine (10 mg/kg) and exposed to extinction of CPP (two sessions per week). When extinction was achieved, each group received the corresponding treatment before the reinstatement test. In experiment 1, six groups were used: vehicle+saline (Veh+Sal), 5 mg/kg cocaine alone (Veh+Coc) or with CBD 30 or 60 mg/kg (CBD30+Coc, CBD60+Coc) and CBD alone (CBD30+Sal, CBD60+Sal). In experiment 2, four groups were used: exploration (Veh+Expl), social defeat (Veh+SD) and social defeat with CBD (CBD30+SD and CBD60+SD). Furthermore, the relative gene expression of the dopamine transporter (DAT) in the ventral tegmental area was measured. Results: All mice acquired cocaine CPP and extinguished it after three or four weeks. Only the groups treated with cocaine priming (Veh+Coc) or exposed to social defeat (Veh+SD) showed reinstatement of CPP. Interestingly, CBD itself did not induce reinstatement and blocked the reinstating effects of cocaine priming and social defeat. Furthermore, cocaine priming increased DAT gene expression in the ventral tegmental area and CBD completely reversed this effect. Conclusion: These results suggest that CBD could reduce reinstatement to cocaine seeking after a period of abstinence.

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Section: Discussioncontrasting

confidence: 81%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

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Cannabidiol prevents priming- and stress-induced reinstatement of the conditioned place preference induced by cocaine in mice

et al. 2021

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“…A growing number of preclinical studies investigated the therapeutic potential (Breslin, Johnson, & Lynch, 2010; Cagetti et al, 2004; Chen & Holmes, 2009; Farook, Morrell, Lewis, Littleton, & Barron, 2007; Hargreaves & McGregor, 2007; Lynch, Bond, Breslin, & Johnson, 2011; Moore, Protzuk, Johnson, & Lynch, 2014) and pitfalls (Arenas et al, 2016) of topiramate as innovative treatment for drug abuse. A range of clinical studies focusing on various addictive drugs suggest that topiramate not only reduces mean consumption levels, but also reduces heavy consumption days and promotes and maintains abstinence (for a review see Thorens et al, 2011).…”

Section: Discussionmentioning

confidence: 99%

Topiramate reduces basal anxiety and relieves ethanol withdrawal-induced anxious behaviors in male rats.

Junqueira-Ayres

Asth

Ayres

et al. 2017

Experimental and Clinical Psychopharmacology

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Anxiety disorders are associated with increased impairments in psychosocial functioning, work productivity and health-related quality of life. In addition, anxiety is a common symptom of ethanol withdrawal and it strongly contributes to relapse. Benzodiazepines are frequently prescribed for relief of anxiety and ethanol withdrawal symptoms but considerable side effects, such sedation, tolerance and dependence, are observed during treatment. Therefore, better drugs are needed for the treatment of anxiety states. The purpose of this study was to investigate whether topiramate would reduce basal levels of anxiety and ethanol-withdrawn induced anxiety in male rats; the elevated plus maze (EPM) was used as an animal model of anxiety. In Experiment 1, topiramate (0, 10, and 40 mg/kg, i.g.) and diazepam (1 mg/kg, i.p.) was acutely and repeatedly administered to naive rats. In Experiments 2 and 3, topiramate (0 or 40 mg/kg, i.g.) was acutely and chronically administered in early (72 hr after ethanol removal) and protracted (21 days after ethanol removal) ethanol-withdrawn rats, respectively. Acute and repeated topiramate treatment induced anxiolytic-like effects in naive rats. Early ethanol withdrawal increased anxiety, and acute topiramate administration counteracted the anxiogenic-like effects of ethanol removal. Protracted withdrawal did not produce lasting changes in anxiety but topiramate was equally effective at reducing anxiety in ethanol-withdrawn and control animals. Importantly, no signs of tolerance to the anxiolytic effects of topiramate were observed. In conclusion, these data support a role for topiramate in the treatment of basal levels of anxiety and ethanol withdrawal-induced anxiety. (PsycINFO Database Record

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“…The two groups of offspring were housed with dams until three weeks postnatal. PNS and control group were tested with a battery for depression-like behaviors at postnatal day (PND) 28 (juvenile) and 60 (adulthood) …”

Section: Methodsmentioning

confidence: 99%

Rapid and Prolonged Antidepressant-like Effect of Crocin Is Associated with GHSR-Mediated Hippocampal Plasticity-related Proteins in Mice Exposed to Prenatal Stress

Wü

Xiao

Shan

et al. 2020

ACS Chem. Neurosci.

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Prenatal stress (PNS) has a prolonged and adverse effect on offspring, leading to a significantly increased vulnerability to developing depression in their later life. Traditional therapies have delayed onset and limited efficacy; thus, it remains an urgent need to find novel medications with fast-onset and high-efficacy potentials. Crocin, with its structure clearly examined, has shown antidepressant-like effects. However, few studies extensively investigated its effect especially in mice exposed to PNS. Using an established PNS model, we tested whether crocin could have a rapid and persistent antidepressant-like effect in PNS mice. Growth hormone secretagogue receptor (GHSR) and phosphoinositide 3-kinase (PI3K) inhibitors were used to test their effects in antidepressant-like effect of crocin. Hippocampal GHSR-PI3K signaling was examined both in PNS mice treated with a single dose of crocin and in combination of GHSR inhibitor. PNS mice showed depression-like behaviors at juvenile and adulthood, and crocin induced an instant and persistent antidepressant-like response in PNS mice in a dose-dependent manner. Moreover, crocin increased the expression of hippocampal synaptic plasticityassociated proteins through the restoration of GHSR-PI3K signaling. Inhibitions of both GHSR and PI3K abolished the effect of crocin in alleviating depressive-like behaviors. More importantly, GHSR inhibitor JMV2959 blocked the enhanced expression of hippocampal plasticity-related proteins induced by crocin. The present study demonstrated that crocin induced a fast-onset and prolonged antidepressant effect in PNS mice and suggested that GHSR-PI3K signaling may play a key role in crocin's effect at least partially by a restoration of hippocampal synaptic plasticity-associated proteins.

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Topiramate increases the rewarding properties of cocaine in young-adult mice limiting its clinical usefulness

Cited by 6 publications

References 38 publications

Cannabidiol prevents priming- and stress-induced reinstatement of the conditioned place preference induced by cocaine in mice

Cannabidiol prevents priming- and stress-induced reinstatement of the conditioned place preference induced by cocaine in mice

Topiramate reduces basal anxiety and relieves ethanol withdrawal-induced anxious behaviors in male rats.

Rapid and Prolonged Antidepressant-like Effect of Crocin Is Associated with GHSR-Mediated Hippocampal Plasticity-related Proteins in Mice Exposed to Prenatal Stress

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