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Prior exposure to stress delays extinction but does not modify reinstatement of nicotine-induced conditioned place preference
Le?o, Rodrigo M;Cruz, Fábio C;Planeta, Cleopatra S;
Psychology & Neuroscience , 2010, DOI: 10.3922/j.psns.2010.1.006
Abstract: studies in humans suggest that exposure to stress is related to relapse to tobacco use. the reinstatement of conditioned place preference (cpp) provides a simple, noninvasive and easy approach to investigate the mechanisms for drug relapse. the present study investigated whether repeated exposure to stress could change the extinction and reinstatement of nicotine-induced cpp. adult male wistar were exposed to restraint-stress for 2 hours/daily for 7 days, while the control-group was left undisturbed during this period. one day after the last stress session the cpp protocol was carried out. nicotine produced a place preference to the compartment paired with its injections during conditioning (.16 mg/kg, s.c.; four drug sessions). once established, nicotine place preference was extinguished by alternate exposure to each compartment after a saline injection (four exposures to each compartment). the animals that did not show extinction of cpp were submitted to two other extinction sessions. following this extinction phase, the reinstatement of place conditioning was investigated following a priming injection of nicotine. both control and stress groups showed reinstatement of cpp. the percentage of rats from the stress group that extinguished nicotine-cpp in the first and second test was lower as compared to the control group. in conclusion, stress delayed the extinction of the nicotine-induced cpp, but did not modify the reinstatement.
Effect of the CB1 cannabinoid agonist WIN 55212-2 on the acquisition and reinstatement of MDMA-induced conditioned place preference in mice
Carmen Manzanedo, Marta Rodríguez-Arias, Manuel Daza-Losada, Concepción Maldonado, María A Aguilar, José Mi?arro
Behavioral and Brain Functions , 2010, DOI: 10.1186/1744-9081-6-19
Abstract: In the first experiment adolescent mice were initially conditioned with 1.25, 2.5 or 5 mg/kg of MDMA or 0.1 or 0.5 mg/kg of WIN and subsequently with both drugs. Reinstatement of the extinguished preference by priming doses was performed in the groups that showed CPP. In the second experiment, animals were conditioned with 2.5 or 5 mg/kg of MDMA and, after extinction, reinstatement of the preference was induced by 0.5 or 0.1 mg/kg of WIN.A low dose of WIN 55212-2 (0.1 mg/kg) increased the rewarding effects of low doses of MDMA (1.25 mg/kg), although a decrease in the preference induced by MDMA (5 and 2.5 mg/kg) was observed when the dose of WIN 55212-2 was raised (0.5 mg/kg). The CB1 antagonist SR 141716 also increased the rewarding effects of the lowest MDMA dose and did not block the effects of WIN. Animals treated with the highest WIN dose plus a non-neurotoxic dose of MDMA exhibited decreases of striatal DA and serotonin in the cortex. On the other hand, WIN 55212-2-induced CPP was reinstated by priming injections of MDMA, although WIN did not reinstate the MDMA-induced CPP.These results confirm that the cannabinoid system plays a role in the rewarding effects of MDMA and highlights the risks that sporadic drug use can pose in terms of relapse to dependence. Finally, the potential neuroprotective action of cannabinoids is not supported by our data; on the contrary, they are evidence of the potential neurotoxic effect of said drugs when administered with MDMA.Numerous reports indicate that MDMA users consume other psychoactive drugs, among which cannabis is one of the most common. Findings regarding concomitant abuse of MDMA and cannabis are similar in different countries, ranging from between 73% and 100% [for review see [1,2]]. Several studies of the prolonged combined use of MDMA and cannabis have highlighted an association with a variety of psychological problems, including elevated impulsiveness, anxiety and psychotic behavior [3].MDMA is an indirect monoami
Previous exposure to stress delays the extinction but does not modify the reinstatement of the nicotine- induced conditioning place preference
Rodrigo Molini Le?o,Fábio Cardoso Cruz,Cleopatra da Silva Planeta
Psychology & Neuroscience , 2010,
Abstract: Studies in humans suggest that exposure to stress is related to relapse to tobacco use. The reinstatement of conditioned place preference (CPP) provides a simple, noninvasive and easy approach to investigate the mechanisms for drug relapse. The present study investigated whether repeated exposure to stress could change the extinction and reinstatement of nicotine-induced CPP. Adult male Wistar were exposed to restraint-stress for 2 hours/daily for 7 days, while the control-group was left undisturbed during this period. One day after the last stress session the CPP protocol was carried out. Nicotine produced a place preference to the compartment paired with its injections during conditioning (.16 mg/kg, s.c.; four drug sessions). Once established, nicotine place preference was extinguished by alternate exposure to each compartment after a saline injection (four exposures to each compartment). The animals that did not show extinction of CPP were submitted to two other extinction sessions. Following this extinction phase, the reinstatement of place conditioning was investigated following a priming injection of nicotine. Both control and stress groups showed reinstatement of CPP. The percentage of rats from the stress group that extinguished nicotine-CPP in the first and second test was lower as compared to the control group. In conclusion, stress delayed the extinction of the nicotine-induced CPP, but did not modify the reinstatement.
Study of the effects of intra-nucleus accumbens shell injections of alcohlic extract of Crocus sativus on the acquisition and expression of morphine-induced conditioned place preference in rats
Narges-al-sadat Mojabi,Akram Eidi,Mohammad Kamalinejad,Ali Khoshbaten
Physiology and Pharmacology , 2008,
Abstract: Background: Previous studies have confirm the effects of water extract of Crocus sativus on the euphoric and behavioral properties of morphine in mice. Objective: In the present study, the effects of intra-accumbal administration of alcohol extract of Crocus sativus stigma on the acquisition and expression of morphine-induced conditioned place preference (CPP) in male Wistar rats (250-300 g) were investigated. Material and Methods: This experimental study was conducted on the 78 male rats that were divided in 18 groups (n=6/group). In a pilot study, different doses of morphine (0.5, 1, 2.5, 5, 7.5 and 10 mg/kg) were injected to the animals for evaluation of the drug's ability to induction of place preference. In the second phase of the experiments, the extract of the C. sativus (1, 5 and 10 μg/rat), was administered into the nucleus accumbens shell during or after induction of morphine CPP. Then, CPP were tested in the animals. One-way Analysis of Variance (ANOVA) was proformed for statistical procedure. Results: Administration of morphine (0.5, 1, 5, 7.5 and 10 mg/kg), indcreased the time spend in the compartment paired with morphine (i.e. conditioned place preference-CPP). The increament was significant for the dose 10 mg/kg of morphine. Injection of the same doses of the extract (1, 5 and 10 μg/rat) 5 min before morphine (10 mg/kg) administration, caused a decrease in the time spent in drug-paired side in doses 5 and 10 μg/rat of the extract. In addition, injection of the plant extract (1, 5 and 10 μg/rat) in to the shell part of nucleus accumbens in the test day to the animals in which reveived morphine (10 mg/kg) in the conditioning days decreased the expression of morphine CPP in the animals which was statisticaly significant for doses 5 and 10 μg/rat of the extract. Conclusion: It could be concluded that intra-accumbens shell compartment njection of the alcoholic extract of C sativus can inhibit the acquisition and expression of morphine-induced CPP and shift it to the aversive state in rats. .
Inactivation of the Nucleus Accumbens Core or Medial Shell Attenuates Reinstatement of Sugar-Seeking Behavior following Sugar Priming or Exposure to Food-Associated Cues  [PDF]
Peagan Lin, Wayne E. Pratt
PLOS ONE , 2014, DOI: 10.1371/journal.pone.0099301
Abstract: Re-exposure to either palatable food or to conditioned stimuli associated with food is known to reinstate food-seeking after periods of abstinence. The nucleus accumbens core and shell are important for reinstatement in both food- and drug-seeking paradigms, although their potential differential roles have been difficult to delineate due to methodological differences in paradigms across laboratories. The present studies assessed the effects of temporary inactivation of the core or shell on priming- and cue-induced reinstatement of food-seeking in identically-trained rats. Inactivation of either the nucleus accumbens core (Experiment 1A; N = 10) or medial shell (Experiment 1B; N = 12) blocked priming-induced reinstatement in an equivalent manner. Similarly, inactivation of the core or medial shell (Experiments 2A & 2B; N = 11 each) also blocked cue-induced reinstatement, although there was also a significant treatment day X brain region X drug order interaction. Specifically, rats with core inactivation reinstated lever-pressing on the vehicle injection day regardless of whether that was their first or second test, whereas rats that had medial shell inactivation on the first day did not significantly reinstate lever-pressing on the second day of testing (when they received vehicle). Yohimbine, while a reportedly robust pharmacological stressor, was ineffective at inducing reinstatement in the current stress-induced reinstatement procedure. These data suggest that both the nucleus accumbens core and shell serve important roles in reinstatement of food-seeking in response to priming and cues.
Role of the Dopaminergic System in the Acquisition, Expression and Reinstatement of MDMA-Induced Conditioned Place Preference in Adolescent Mice  [PDF]
Antonio Vidal-Infer,Concepción Roger-Sánchez,Manuel Daza-Losada,María A. Aguilar,José Mi?arro,Marta Rodríguez-Arias
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0043107
Abstract: The rewarding effects of 3,4-methylenedioxy-metamphetamine (MDMA) have been demonstrated in conditioned place preference (CPP) procedures, but the involvement of the dopaminergic system in MDMA-induced CPP and reinstatement is poorly understood.
Cocaine-Induced Reinstatement of a Conditioned Place Preference in Developing Rats: Involvement of the D2 Receptor  [PDF]
Kimberly A. Badanich,Cheryl L. Kirstein
Brain Sciences , 2012, DOI: 10.3390/brainsci2040573
Abstract: Reinstatement of conditioned place preferences have been used to investigate physiological mechanisms mediating drug-seeking behavior in adolescent and adult rodents; however, it is still unclear how psychostimulant exposure during adolescence affects neuron communication and whether these changes would elicit enhanced drug-seeking behavior later in adulthood. The present study determined whether the effects of intra-ventral tegmental area (VTA) or intra-nucleus accumbens septi (NAcc) dopamine (DA) D2 receptor antagonist infusions would block (or potentiate) cocaine-induced reinstatement of conditioned place preferences. Adolescent rats (postnatal day (PND 28–39)) were trained to express a cocaine place preference. The involvement of D2 receptors on cocaine-induced reinstatement was determined by intra-VTA or intra-NAcc infusion of the DA D2 receptor antagonist sulpiride (100 μM) during a cocaine-primed reinstatement test (10 mg/kg cocaine, i.p.). Infusion of sulpiride into the VTA but not the NAcc blocked reinstatement of conditioned place preference. These data suggest intrinsic compensatory mechanisms in the mesolimbic DA pathway mediate responsivity to cocaine-induced reinstatement of a conditioned place preference during development.
Effect of Cafeteria Diet History on Cue-, Pellet-Priming-, and Stress-Induced Reinstatement of Food Seeking in Female Rats  [PDF]
Yu-Wei Chen, Kimberly A. Fiscella, Samuel Z. Bacharach, Donna J. Calu
PLOS ONE , 2014, DOI: 10.1371/journal.pone.0102213
Abstract: Background Relapse to unhealthy eating habits is a major problem in human dietary treatment. The individuals most commonly seeking dietary treatment are overweight or obese women, yet the commonly used rat reinstatement model to study relapse to palatable food seeking during dieting primarily uses normal-weight male rats. To increase the clinical relevance of the relapse to palatable food seeking model, here we pre-expose female rats to a calorically-dense cafeteria diet in the home-cage to make them overweight prior to examining the effect of this diet history on cue-, pellet-priming- and footshock-induced reinstatement of food seeking. Methods Post-natal day 32 female Long-Evans rats had seven weeks of home-cage access to either chow only or daily or intermittent cafeteria diet alongside chow. Next, they were trained to self-administer normally preferred 45 mg food pellets accompanied by a tone-light cue. After extinction, all rats were tested for reinstatement induced by discrete cue, pellet-priming, and intermittent footshock under extinction conditions. Results Access to daily cafeteria diet and to a lesser degree access to intermittent cafeteria diet decreased food pellet self-administration compared to chow-only. Prior history of these cafeteria diets also reduced extinction responding, cue- and pellet-priming-induced reinstatement. In contrast, modest stress-induced reinstatement was only observed in rats with a history of daily cafeteria diet. Conclusion A history of cafeteria diet does not increase the propensity for cue- and pellet-priming-induced relapse in the rat reinstatement model but does appear to make rats more susceptible to footshock stress-induced reinstatement.
Identification of Brain Nuclei Implicated in Cocaine-Primed Reinstatement of Conditioned Place Preference: A Behaviour Dissociable from Sensitization  [PDF]
Robyn Mary Brown,Jennifer Lynn Short,Andrew John Lawrence
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0015889
Abstract: Relapse prevention represents the primary therapeutic challenge in the treatment of drug addiction. As with humans, drug-seeking behaviour can be precipitated in laboratory animals by exposure to a small dose of the drug (prime). The aim of this study was to identify brain nuclei implicated in the cocaine-primed reinstatement of a conditioned place preference (CPP). Thus, a group of mice were conditioned to cocaine, had this place preference extinguished and were then tested for primed reinstatement of the original place preference. There was no correlation between the extent of drug-seeking upon reinstatement and the extent of behavioural sensitization, the extent of original CPP or the extinction profile of mice, suggesting a dissociation of these components of addictive behaviour with a drug-primed reinstatement. Expression of the protein product of the neuronal activity marker c-fos was assessed in a number of brain regions of mice that exhibited reinstatement (R mice) versus those which did not (NR mice). Reinstatement generally conferred greater Fos expression in cortical and limbic structures previously implicated in drug-seeking behaviour, though a number of regions not typically associated with drug-seeking were also activated. In addition, positive correlations were found between neural activation of a number of brain regions and reinstatement behaviour. The most significant result was the activation of the lateral habenula and its positive correlation with reinstatement behaviour. The findings of this study question the relationship between primed reinstatement of a previously extinguished place preference for cocaine and behavioural sensitization. They also implicate activation patterns of discrete brain nuclei as differentiators between reinstating and non-reinstating mice.
Effect of filtration on morphine and particle content of injections prepared from slow-release oral morphine tablets
Stuart McLean, Raimondo Bruno, Susan Brandon, Barbara de Graaff
Harm Reduction Journal , 2009, DOI: 10.1186/1477-7517-6-37
Abstract: Injection solutions were prepared from slow-release morphine tablets (MS Contin?) replicating methods used by injecting drug users. Contaminating particles were counted by microscopy and morphine content analysed by liquid chromatography before and after filtration.Unfiltered tablet extracts contained tens of millions of particles with a range in sizes from < 5 μm to > 400 μm. Cigarette filters removed most of the larger particles (> 50 μm) but the smaller particles remained. Commercial syringe filters (0.45 and 0.22 μm) produced a dramatic reduction in particles but tended to block unless used after a cigarette filter. Morphine was retained by all filters but could be recovered by following the filtration with one or two 1 ml washes. The combined use of a cigarette filter then 0.22 μm filter, with rinses, enabled recovery of 90% of the extracted morphine in a solution which was essentially free of tablet-derived particles.Apart from overdose and addiction itself, the harmful consequences of injecting morphine tablets come from the insoluble particles from the tablets and microbial contamination. These harmful components can be substantially reduced by passing the injection through a sterilizing (0.22 μm) filter. To prevent the filter from blocking, a preliminary coarse filter (such as a cigarette filter) should be used first. The filters retain some of the dose, but this can be recovered by following filtration with one or two rinses with 1 ml water. Although filtration can reduce the non-pharmacological harmful consequences of injecting tablets, this remains an unsafe practice due to skin and environmental contamination by particles and microorganisms, and the risks of blood-borne infections from sharing injecting equipment.It is common for many injecting drug users to prepare injections from tablets that are designed for oral administration [1,2]. Tablets contain therapeutically inactive ingredients to facilitate the lubrication, disintegration and dissolution of
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