Characterization of the Neurochemical and Behavioral Effects of the Phenethylamine 2-Cl-4,5-MDMA in Adolescent and Adult Male Rats.

Background: The proliferation of novel psychoactive substances (NPS) in the drug market raises concerns about uncertainty on their pharmacological profile and the health hazard linked to their use. Within the category of synthetic stimulant NPS, the phenethylamine 2-Cl-4,5-methylenedioxymethamphetamine (2-Cl-4,5-MDMA) has been linked to severe intoxication requiring hospitalization. Thereby, the characterization of its pharmacological profile is urgently warranted.

Energy drinks at adolescence: Awareness or unawareness?

Energy drinks (EDs) are beverages similar to soft drinks, characterized by high caffeine concentrations with additional ingredients like taurine and vitamins, marketed for boosting energy, reducing tiredness, increasing concentration, and for their ergogenic effect. The majority of consumers are children, adolescents, and young athletes. Although EDs companies claim about the ergogenic and remineralizing properties of their products, there is a serious lack of evidence at preclinical as well as clinical level to validate their benefits.

Influence of Age and Genetic Background on Ethanol Intake and Behavioral Response Following Ethanol Consumption and During Abstinence in a Model of Alcohol Abuse.

Genetic background and age at first exposure have been identified as critical variables that contribute to individual vulnerability to drug addiction. Evidence shows that genetic factors may account for 40-70% of the variance in liability to addiction. Alcohol consumption by young people, especially in the form of binge-drinking, is becoming an alarming phenomenon predictive of future problems with drinking.

Adolescent cannabis exposure increases heroin reinforcement in rats genetically vulnerable to addiction.

On the basis of epidemiological studies it has been proposed that cannabis use plays a causal role in the abuse of highly addictive drugs (Gateway Hypothesis). However, epidemiological studies are intrinsically unable to provide evidence of causality. Experimental studies can provide this evidence but they are feasible only in animal models and to date such evidence is lacking.

Role of genetic background in the effects of adolescent nicotine exposure on mesolimbic dopamine transmission.

Smoking during adolescence may increase the likelihood to develop nicotine dependence and to abuse other drugs such as cocaine. Despite great efforts to understand underlying neurobiological mechanisms of this progression, less attention has been paid to the role of genetic factors. Here, we investigated the influence of both genetic background and age at first nicotine exposure in the long-lasting effects on mesolimbic dopamine transmission including the increased cocaine-rewarding effect.

Adolescence versus adulthood: Differences in basal mesolimbic and nigrostriatal dopamine transmission and response to drugs of abuse.

Epidemiological studies have shown that people who begin experimenting drugs of abuse during adolescence are more likely to develop substance use disorders, and the earliest is the beginning of their use, the greatest is the likelihood to become dependent. Understanding the neurobiological changes increasing adolescent vulnerability to drug use is becoming imperative. Although all neurotransmitter systems undergo relevant developmental changes, dopamine system is of particular interest, given its role in a variety of functions related to reward, motivation, and decision making.

Widespread reduction of dopamine cell bodies and terminals in adult rats exposed to a low dose regimen of MDMA during adolescence.

Although MDMA (3,4-methylendioxymethamphetamine, ecstasy) neurotoxicity in serotonin neurons is largely recognized in a wide variety of species including man, neurotoxicity in dopamine (DA) neurons is thought to be species-specific. MDMA is mainly consumed by adolescents, often in conjunction with caffeine (Energy Drinks) and this association has been reported to exacerbate MDMA toxic effects. In order to model these aspects of MDMA use, vis-à-vis their impact on DA neurons, we investigated the effects of adolescent exposure to low doses of MDMA (5 mg/kg for 10 days), alone or in combination with caffeine (10 mg/kg) on neuronal and functional DA indices and on recognition memory in adult rats.

Is there a Teratogenicity Risk Associated with Cannabis and Synthetic Cannabimimetics' ('Spice') Intake?

Background: Substance use, including cannabis, has been documented amongst women both in the pre-conception period and during pregnancy, particularly during the 1st trimester, which is clearly the most critical period in the organogenesis. The recent emergence on the drug market of synthetic cannabimimetics/SC ('spice') may represent a new challenge for clinicians.

Objective: A literature overview on the teratogenicity profile of both cannabis and synthetic cannabimimetics was here carried out.

Cannabis; Epidemiological, Neurobiological and Psychopathological Issues: An Update.

Background: Cannabis is the illicit drug with both the largest current levels of consumption and the highest reported lifetime prevalence levels in the world. Across different countries, the prevalence of cannabis use varies according to the individual income, with the highest use being reported in North America, Australia and Europe. Despite its 'soft drug' reputation, cannabis misuse may be associated with several acute and chronic adverse effects.

Fischer 344 and Lewis Rat Strains as a Model of Genetic Vulnerability to Drug Addiction.

Today it is well acknowledged that both nature and nurture play important roles in the genesis of psychopathologies, including drug addiction. Increasing evidence suggests that genetic factors contribute for at least 40-60% of the variation in liability to drug dependence. Human genetic studies suggest that multiple genes of small effect, rather than single genes, contribute to the genesis of behavioral psychopathologies.

Impairment of acquisition of intravenous cocaine self-administration by RNA-interference of dopamine D1-receptors in the nucleus accumbens shell.

Microdialysis during i.v. drug self-administration (SA) have implicated nucleus accumbens (NAc) shell DA in cocaine and heroin reinforcement.

Strain dependence of adolescent Cannabis influence on heroin reward and mesolimbic dopamine transmission in adult Lewis and Fischer 344 rats.

Adolescent Cannabis exposure has been hypothesized to act as a gateway to opiate abuse. In order to investigate the role of genetic background in cannabinoid-opiate interactions, we studied the effect of Δ(9) -tetrahydrocannabinol (THC) exposure of adolescent Lewis and Fischer 344 rats on the responsiveness of accumbens shell and core dopamine (DA), as monitored by microdialysis, to THC and heroin at adulthood. Heroin reward and reinstatement by heroin priming were studied by conditioned place preference (CPP) and cognitive and emotional functions by object recognition, Y maze and elevated plus maze paradigms.

Differential influence of morphine sensitization on accumbens shell and core dopamine responses to morphine- and food-conditioned stimuli.

Rationale: Sensitization of the incentive and dopamine (DA) stimulant properties of drug-conditioned stimuli (CSs) by repeated exposure to drugs of abuse has been assigned an important role in the genesis of drug addiction.

Objective: To test in rats if morphine-induced sensitization potentiates incentive and DA-releasing properties in the nucleus accumbens (NAc) shell and core elicited by presentation of a morphine-conditioned stimulus(CS) and if this property generalizes to a non-drug-(palatable food, Fonzies)-CS.

Methods: Controls and rats previously sensitized by morphine were trained via three daily sessions consisting of a 10-min presentation of CS (Fonzies filled box, FB) followed by s.

Conditioned saccharin avoidance and sensitization to drugs of abuse.

Saccharin avoidance conditioned by drugs of abuse (CSA) has been interpreted as an expression of the appetitive, dopamine-dependent, properties of the drug. Repeated exposure to these drugs induces an increase (sensitization) of their motor stimulant properties associated with differential changes in DA transmission in the NAc shell and core. The present study investigated the changes in drug CSA induced by schedules of repeated drug exposure that induce behavioral sensitization.

Nicotine differentially affects dopamine transmission in the nucleus accumbens shell and core of Lewis and Fischer 344 rats.

Genetic factors are known to affect the reinforcing properties of nicotine. Thus, inbred Lewis rats have been reported to be more sensitive to nicotine compared to Fischer 344 rats in self-administration, conditioned place preference and drug discrimination paradigms. In order to clarify the mechanisms of these differences we investigated, by means of dual probe microdialysis, the effect of different doses of nicotine (0.

Behavioral sensitization to delta 9-tetrahydrocannabinol and cross-sensitization with morphine: differential changes in accumbal shell and core dopamine transmission.

Although cannabinoid-induced behavioral sensitization and cross-sensitization with opiates has been recently demonstrated, no information is available on the associated state and responsiveness of dopamine (DA) transmission in the nucleus accumbens (NAc) shell and core. In this study we investigate by means of dual probe microdialysis, the effect of exposure to a sensitizing regimen of Delta(9)-tetrahydrocannabinol (Delta(9)-THC) and morphine on the extracellular concentrations of DA under basal conditions and after challenge with Delta(9)-THC and morphine in the NAc shell and core. Different groups of male Sprague-Dawley rats were administered twice daily for 3 days with increasing doses of Delta(9)-THC (2, 4, and 8 mg/kg i.

Long-term increase in GAD67 mRNA expression in the central amygdala of rats sensitized by drugs and stress.

Repeated administration of addictive drugs and prolonged exposure to stressful stimuli induce sensitization to their behavioural stimulant properties. In this study, male Sprague-Dawley rats were repeatedly exposed to morphine [twice a day for 3 days at increasing doses, 10, 20, 40 mg/kg subcutaneously (s.c)], amphetamine (1 mg/kg s.

Differences in dopamine responsiveness to drugs of abuse in the nucleus accumbens shell and core of Lewis and Fischer 344 rats.

The use of inbred rat strains provides a tool to investigate the role of genetic factors in drug abuse. Two such strains are Lewis and Fischer 344 rats. Although several biochemical and hormonal differences have been observed between Lewis and Fischer 344 strains, a systematic comparison of the effect of different drugs of abuse on dopamine (DA) transmission in the shell and core of the nucleus accumbens of these strains is lacking.

Effect of 3,4-methylendioxymethamphetamine (MDMA, "ecstasy") on dopamine transmission in the nucleus accumbens shell and core.

It is known that most of drugs abused by humans preferentially stimulate dopamine transmission in the shell subdivision of the nucleus accumbens as compared to the core. The aim of the present study was to evaluate whether this applies also to intravenous 3,4-methylendioxymethamphetamine (MDMA, "ecstasy") administered at doses that sustain self-administration behavior in rats. The effect of 0.

Dopamine and drug addiction: the nucleus accumbens shell connection.

Microdialysis studies in animals have shown that addictive drugs preferentially increase extracellular dopamine (DA) in the n. accumbens (NAc). Brain imaging studies, while extending these finding to humans, have shown a correlation between psychostimulant-induced increase of extracellular DA in the striatum and self-reported measures of liking and 'high' (euphoria).

Selective psychostimulant sensitization by food restriction: differential changes in accumbens shell and core dopamine.

We have recently reported that behavioural sensitization to morphine, amphetamine, cocaine and nicotine is associated with an increased response of dialysate dopamine to the same drugs in the nucleus accumbens core and/or a reduced response in the shell. Prolonged exposure to stressful stimuli also induces behavioural sensitization to drugs of abuse. We therefore investigated the effect of different drugs of abuse on behaviour and on dopamine transmission in the nucleus accumbens shell and core of rats stressed by 1 week schedule of food restriction.