Carmen Manzanedo

Universitat de València

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José Miñarro

Universitat de València

Marta Rodríguez‐Arias

Universitat de València

M.A. Aguilar

Universitat de València

M. Carmen Arenas

Universitat de València

Bruno Ribeiro Do Couto

Universidade do Porto

Marina D. Reguilón

Universitat de València

C. Roger-Sánchez

Universitat de València

M. Carmen Blanco-Gandía

Universidad de Zaragoza

Sergio Pujante-Gil

Universitat de València

Carmen Ferrer‐Pérez

Universitat de València

Cooperative Institutions

Universitat de València

Instituto de Salud Carlos III

Universidad de Zaragoza

Generalitat Valenciana

Jackson and Tull (United States)

Federación Española de Enfermedades Raras

Universidad de Málaga

Universidad Complutense de Madrid

Consejo Superior de Investigaciones Científicas

Valencia Catholic University Saint Vincent Martyr

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Individual differences in the induction of sensitisation or tolerance to the motor effects of morphine in mice

Neuroscience Research Communications (2001)

Carmen Manzanedo M.A. Aguilar Marta Rodríguez-Árias José Miñarro

Abstract Acute morphine administration produces hyperactivity in most strains of mice and some studies indicate that repeated treatment can induce a potentiation of this effect (sensitisation). With the object of determining whether the hyperactivity induced by morphine in OF1 mice shows sensitisation after repeated administration, we tested the effect of the pre‐exposure to six daily injections of morphine on the subsequent hyperactivity induced by the same dose of this drug. Animals were treated with 40 mg/kg of morphine for seven days. After the last injection they were tested in an actimeter at different points at time (15, 30, 45 and 60 min). This repeated schedule of treatment produced sensitisation in some animals but tolerance in others. These results suggest the existence of great individual differences in the motor effects of repeated morphine administration and that the development of sensitisation and tolerance in outbred mice may be subjected to genetic variation.

10.1002/nrc.1026

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Citations (2)

Prepulse inhibition can predict the motivational effects of cocaine in female mice exposed to maternal separation

Behavioural Brain Research (2021)

M. Carmen Arenas Adriana Castro‐Zavala Ana Martín‐Sánchez M. Carmen Blanco-Gandía José Miñarro

The prepulse inhibition (PPI) of the startle response can identify the rodents that are more sensitive to the effects of cocaine. Mice with a lower PPI presented a higher vulnerability to the effects of cocaine and a higher susceptibility to developing a substance use disorder (SUD). Maternal separation with early weaning (MSEW) is a relevant animal model to induce motivational alterations throughout life. Nevertheless, only a few studies on females exist, even though they are more vulnerable to stress- and cocaine-related problems. Hence, the aim of the present study was to evaluate the ability of PPI to identify females with a greater vulnerability to the long-term consequences of early stress on the motivational effects of cocaine. Female mice underwent MSEW and were classified according to their high or low PPI. They were then assessed in the cocaine-induced locomotor sensitization test, the conditioned place preference paradigm or the operant self-administration paradigm. Additionally, they were also evaluated in the passive avoidance task, the tail-suspension and the splash tests. The results revealed that the females with lower PPI presented higher consequences of MSEW on the effects of cocaine and showed an increase in anhedonia-like behaviours. Our findings support that a PPI deficit could represent a biomarker of vulnerability to the effects of cocaine induced by MSEW.

Anhedonia

Vulnerability

Startle response

Conditioned place preference

Stimulant

10.1016/j.bbr.2021.113545

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Citations (3)

Novelty Seeking

Springer eBooks (2016)

M. C. Arenas Carmen Manzanedo

10.1007/978-3-319-28099-8_1095-1

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Citations (2)

Rhodiola roseaImpairs Acquisition and Expression of Conditioned Place Preference Induced by Cocaine

Evidence-based Complementary and Alternative Medicine (2013)

Federica Titomanlio Carmen Manzanedo Marta Rodríguez-Árias Laura Mattioli Marina Perfumi

A novel approach to the treatment of adverse effects of drugs of abuse is one which makes use of natural products. The present study investigated the effect of Rhodiola rosea L. hydroalcoholic extract (RHO) on cocaine-induced hyperactivity and conditioned place preference (CPP) in mice. In a first experiment, mice received RHO (15, 20 or 25 mg/kg, IG), cocaine (25 mg/kg, i.p.) (COC), or a combination of both drugs (COC + RHO15, COC + RHO20, and COC + RHO25), and their locomotor activity was evaluated. In a second experiment, the effects of RHO on the acquisition, expression, and reinstatement of cocaine CPP (induced by drug priming or social defeat stress) were evaluated. RHO alone did not increase activity but potentiated the hyperactivity induced by cocaine. Rhodiola did not induce motivational effects by itself but attenuated the acquisition and expression of cocaine-induced CPP. Moreover, it was found that RHO did not block reinstatement. The results indicate that RHO is effective in reducing the rewarding properties of cocaine but is ineffective in preventing priming or stress-induced cocaine reinstatement. In light of these findings, the benefits of Rhodiola rosea L. as a treatment of cocaine addiction would seem to be limited.

Rhodiola Rosea

Conditioned place preference

Rhodiola

Priming (agriculture)

10.1155/2013/697632

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Citations (19)

Preclinical evidence of new opioid modulators for the treatment of addiction

Expert Opinion on Investigational Drugs (2010)

Marta Rodríguez-Árias M.A. Aguilar Carmen Manzanedo José Miñarro

Importance of the field: Addiction to opiates is one of the most severe forms of substance dependence, and despite a variety of pharmacological approaches to treat it, relapse is observed in a high percentage of subjects. New pharmacological compounds are necessary to improve the outcome of treatments and reduce adverse side effects. Moreover, drugs that act on the opioid system can also be of benefit in the treatment of alcohol or cocaine addiction.

Opiate

Pharmacotherapy

Physical dependence

10.1517/13543784.2010.500612

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Citations (12)

Adolescent Exposure to the Synthetic Cannabinoid WIN 55212-2 Modifies Cocaine Withdrawal Symptoms in Adult Mice

International Journal of Molecular Sciences (2017)

M.A. Aguilar Juan Ledesma Marta Rodríguez-Árias Carles Penalva Carmen Manzanedo

Chronic cannabinoid consumption is an increasingly common behavior among teenagers and has been shown to cause long-lasting neurobehavioral alterations. Besides, it has been demonstrated that cocaine addiction in adulthood is highly correlated with cannabis abuse during adolescence. Cocaine consumption and subsequent abstinence from it can cause psychiatric symptoms, such as psychosis, cognitive impairment, anxiety, and depression. The aim of the present research was to study the consequences of adolescent exposure to cannabis on the psychiatric-like effects promoted by cocaine withdrawal in adult mice. We pre-treated juvenile mice with the cannabinoid CB1 receptor agonist WIN 55212-2 (WIN) and then subjected them to a chronic cocaine treatment during adulthood. Following these treatments, animals were tested under cocaine withdrawal in the following paradigms: pre-pulse inhibition, object recognition, elevated plus maze, and tail suspension. The long-term psychotic-like actions induced by WIN were not modified after cocaine cessation. Moreover, the memory impairments induced by cocaine withdrawal were not altered by previous adolescent WIN intake. However, WIN pre-treatment prevented the anxiogenic effects observed after cocaine abstinence, and led to greater depressive-like symptoms following cocaine removal in adulthood. This study is the first to show the long-lasting behavioral consequences of juvenile exposure to WIN on cocaine withdrawal in adult mice.

Anxiogenic

Elevated plus maze

Methamphetamine

10.3390/ijms18061326

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Citations (16)

Ethanol intake in male mice exposed to social defeat: Environmental enrichment potentiates resilience

Neurobiology of Stress (2021)

Marina D. Reguilón Carmen Ferrer‐Pérez Carmen Manzanedo José Miñarro Marta Rodríguez-Árias

Large preclinical evidence shows that exposure to social defeat (SD) increases vulnerability to drug abuse, increasing the consumption of ethanol. However, not all subjects are equally affected by the changes induced by stress. Previous reports have evidenced that the resilient phenotype to depressive-like behaviors after SD is associated with the resistant phenotype to cocaine-increased rewarding effects and the smaller neuroinflammatory response. The aim of the present study was to further clarify whether the resilient profile to depressive-like behavior also predicts a protection against the increase in ethanol intake induced by SD. The neuroinflammatory profile was studied after the end of the oral ethanol self-administration (SA) procedure, measuring levels of the pro-inflammatory cytokine IL-6 and the chemokine CX3CL1 or fractalkine in the striatum and prefrontal cortex. Previous studies have shown that environmental enrichment (EE) is an effective mechanism to dimish the detrimental effects of social stress. In a second study, we aimed to evaluate if EE housing before exposure to SD could potentiate resilience. Our results showed that mice with a phenotype susceptible to SD-induced depressive-like behaviors showed increased ethanol consumption and increased neuroinflammatory signaling. In contrast, despite the lack of effect on depressive-like behaviors, defeated mice previously housed under EE conditions did not show an increase in ethanol SA or an increase in immune response. To sum up, the resilient phenotype to SD develops at different levels, such as depressive-like behaviors, ethanol consumption and the neuroinflammatory response. Our results also point to the protective role of EE in potentiating resilience to SD effects.

Social defeat

Self-administration

Environmental Enrichment

10.1016/j.ynstr.2021.100413

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Citations (12)

Novelty Seeking

Springer eBooks (2020)

M. C. Arenas Carmen Manzanedo

10.1007/978-3-319-24612-3_1095

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Citations (0)

Social stress is as effective as physical stress in reinstating morphine-induced place preference in mice

Psychopharmacology (2006)

Bruno Ribeiro Do Couto M.A. Aguilar Carmen Manzanedo Marta Rodríguez-Árias Antonio Armario

Conditioned place preference

Extinction (optical mineralogy)

Social defeat

Social Stress

Stressor

Self-administration

Agonistic behaviour

10.1007/s00213-006-0345-z

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Citations (111)

Sex differences in behavioral traits related with high sensitivity to the reinforcing effects of cocaine

Behavioural Brain Research (2021)

Sergio Pujante-Gil Carmen Manzanedo M. Carmen Arenas

Cocaine is the most prevalent illegal stimulant drug in Europe among the adult population. Its abuse is characterized by a faster substance abuse disorder (SUD) development than other drugs, with high vulnerability to relapse. However, there does not exist an effective treatment for cocaine dependence. Sex differences have been reported in psychological disorders including SUD. For this reason, it is essential to identify risk factors that predict susceptibility or resilience to cocaine addiction for the development of effective prevention strategies considering sex differences. In the present study, the main objective was to determine more sensitive phenotypes to the conditioned reinforcing effects of cocaine in both sexes. Anxiety-like behavior and the locomotor response to novelty were evaluated in the elevated plus maze, and despair in the tail suspension test, as well as vulnerability traits linked with a high sensitivity to the reinforcing effects of a subthreshold dose of cocaine (1 mg/kg) in the conditioned place preference (CPP) paradigm in male and female mice. Our results indicated that only female mice with high anxiety, low locomotor response to novelty or low despair levels acquired CPP induced by cocaine, while male mice with low anxiety, high locomotor response to novelty or high despair levels presented a higher susceptibility to the rewarding effects of cocaine than others. These sex differences in the results reveal an opposite pattern in males and females on the relationship between anxiety- and depressive-like behaviors and cocaine vulnerability, demonstrating the need to include female mice in preclinical studies.

Conditioned place preference

Stimulant

Vulnerability

Anhedonia

Elevated plus maze

10.1016/j.bbr.2021.113505

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Citations (4)