Raymond J.M. Niesink

The neurobiology of social play behavior in rats

Social play behavior is one of the earliest forms of non-mother-directed social behavior appearing in ontogeny in mammalian species. During the last century, there has been a lot of debate on the significance of social play behavior, but behavioral studies have indicated that social play behavior is a separate and relevant category of behavior. The present review provides a comprehensive survey of studies on the neurobiology of social play behavior. Evidence is presented that opioid and dopamine systems play a role in the reward aspect of social play behavior. The role of cholinergic, noradrenergic and opioid systems in attentional processes underlying the generation of social play behavior and the involvement of androgens in the sexual differentiation of social play behavior in rats is summarized. It is concluded that there is not only behavioral, but also neurobiological evidence to suggest that social play behavior represents a separate category of behavior, instead of a precursor for adult social, sexual or aggressive behavior.

Instability of the ecstasy market and a new kid on the block: mephedrone

Recently, several reports have indicated instability of the ecstasy market in the Netherlands and other EU countries. In the current study, we demonstrate this instability in the Netherlands, showing a decrease of ecstasy tablets containing 3,4-methylenedioxymetamphetamine (MDMA) by more than 50% in 2009. In addition, we describe a partial replacement of MDMA in tablets sold as ecstasy by a previously unseen substance, mephedrone (or 4-methylmethcathinone). Mephedrone was quantified and ecstasy tablets contained between 96 and 155u2009mg of this new compound. So far, no studies about mephedrone’s effects have been published. For this study, we gathered information on the acute subjective effects of mephedrone from 70 regular ecstasy users. Overall, the majority of users considered the effects enjoyable. Mephedrone seemed to evoke effects similar to other amphetamine type psychostimulants, including MDMA. In contrast to MDMA, however, mephedrone induced strong feelings of craving in most users. If the unstable ecstasy market situation persists, the potential of mephedrone to substitute for MDMA might be substantial. Mephedrone, sold as ecstasy, is therefore likely to be a valid cause for health concern.

Influence of environmental factors on social play behavior of juvenile rats

The effects of light level and familiarity to the testing environment on social behaviors related and unrelated to play were investigated in juvenile rats accustomed to dim light conditions. Pinning, a measure characteristic for social play in rats, was completely suppressed under intense light conditions. Following/chasing and boxing/wrestling, social behaviors related to play, were also decreased under intense light. Of the measures of social behavior not related to play, contact behavior was decreased under intense light whereas social exploration was hardly affected. Levels of social exploration and following/chasing gradually declined during the 15-min test period. Frequency of contact behavior decreased, whereas duration increased with time. Under dim light conditions, unfamiliarity to the test cage suppressed pinning and boxing/wrestling but not the other social behaviors in the first part of the test period. These findings show that social behavior in juvenile rats, as in adult rats, can be influenced by light level and familiarity to the test cage. Social behaviors related and unrelated to play seem to be differentially influenced by environmental stimuli.

Effects of morphine on different aspects of social play in juvenile rats

To clarify the influence of opioids on social play, the effects of morphine on playful and non-playful social behavior in juvenile rats was investigated under different conditions. Environmental variables employed were different (dim and intense) levels of illumination during testing, familiarity to the test cage, and different periods of social isolation prior to testing. Under dim light conditions, morphine markedly increased playful social behavior, such as pinning, boxing/wrestling and following/chasing, whereas non-playful social behavior such as social exploration and contact behavior was hardly affected. This effect of morphine was independent of duration of previous isolation and dose-dependent, with a maximal effect at 1.0 mg/kg. The mechanism of this effect is interpreted as an action on the rewarding aspects of play. A dose of 0.1 mg/kg of morphine abolished the initial suppression of play induced by unfamiliarity to the test cage, without influencing total levels of play. This may be an effect of morphine on the integration of sensory stimuli. Under intense light conditions, where playful behavior was completely suppressed, morphine itself hardly affected such behavior, but decreased some aspects of non-playful social behavior. These results suggest that in juvenile rats playful and non-playful forms of social behavior are differentially regulated. In addition, opioid systems may be involved at different levels in the regulation of social play.

μ- and κ-opioid receptor-meiated opioid effects on social play in juvenile rats

Previously, morphine has been shown to influence social play behavior in rats on two levels. An increasing effect on social play was interpreted as an effect on the rewarding aspects of social play. A lower dose of morphine abolished the effects of an unfamiliar environment on social play, supposedly by affecting the integration of environmental stimuli. In the present study the effects of receptor-specific opioid drugs on social play and measures of social behavior unrelated to play were investigated. Fentanyl, a μ-opioid receptor agonist, seemingly mimicked both effects of morphine. The μ-opioid receptor antagonist, β-funaltrexamine, decreased social play, although a low dose of this drug increased it. BUBUC (Tyr-d-Cys(StBu)-Gly-Phe-Leu-Thr(OtBu)) and naltrindole, a δ-opioid receptor agonist and δ-opioid receptor antagonist, respectively, had no effects on social behavior. The κ-opioid receptor agonist, U50,488H (trans-3,4-dichloro-N-methyl-N-[2-(1-pyrrolidinyl)-cyclohexyl]-benzenea-cetamide), dose dependently suppressed all measures of social behavior. The κ-opioid receptor antagonist, nor-binaltorphimine, abolished the effects of an unfamiliar environment on social play. These studies suggest that the opioidergic effect on social play is mediated through μ- and κ-opioid receptor systems.

An analysis of cocaine powder in the Netherlands: content and health hazards due to adulterants

AIMSnTo report on trends in the content and adulterants present in street cocaine (powder) in the Netherlands and to describe the associated health hazards.nnnDESIGN AND PARTICIPANTSnDrug consumers handed in samples of cocaine powder from 1999 to 2007 for analysis. Reports were compiled of users experiences with the samples received.nnnMEASUREMENTS AND ANALYSISnLinear regression analysis was used to assess the trend in adulterated cocaine powder across the study period, and comparison of reported adverse effects of adulterated with those of unadulterated cocaine by Fishers exact test.nnnFINDINGSnThere has been a statistically significant upward trend in the occurrence of adulterated cocaine powder over the years. Adulterated cocaine was associated more frequently with reported adverse effects than unadulterated cocaine. Phenacetin, hydroxyzine and diltiazem appeared to be three adulterants contributing to these adverse effects.nnnCONCLUSIONSnAn increase in adulterants was detected in the analysed cocaine powder between 1999 and 2007. This increase is associated with relatively more adverse effects with cocaine use. The cardiac and hallucinatory effects that were reported more frequently are not understood clearly. Adverse effects are likely to be due to several factors, including interactions of adulterants with cocaine and the route of administration.

Content of ecstasy in the Netherlands: 1993-2008.

AIMSnThe present paper outlines the results of analyses carried out on the content of tablets sold as ecstasy, collected in the Netherlands by the Drugs Information Monitoring System (DIMS) from January 1993 to December 2008.nnnMETHODSnDuring a period of 16 years, the DIMS analysed the content of 33 006 tablets sold as ecstasy that were handed in by numerous individual (potential) substance users. The DIMS results were compared with the results from various seized tablets to determine whether the DIMS is a monitor of the ecstasy consumer market.nnnRESULTSnThe DIMS system appears to be a market monitor that gives an accurate reflection of what is actually available on the hidden Dutch ecstasy market. During 16 years of monitoring, the purity [tablets containing only 3,4-methylenedioxymethamphetamine (MDMA)] was lowest around 1997. During this time-period many tablets contained other substances in addition to or instead of MDMA [e.g. 3,4-methylene-dioxyamphetamine (MDA), 3,4-methylene-dioxyethylamphetamine (MDEA) and N-methyl-a-(1,3-benzodixol-5-yl)-2-butamine (MBDB), amphetamine and caffeine]. From 1998 to 2008, the number of high-dose tablets (> or =106 mg MDMA per tablet) gradually increased. The same holds true for the proportion of tablets that contained only MDMA, reaching the highest levels in 2000 and 2004. After 2004, the purity of ecstasy tablets decreased again, caused mainly by a growing proportion of tablets containing meta-chlorophenylpiperazine (mCPP).nnnCONCLUSIONSnThe DIMS results provide valuable qualitative information on the content of ecstasy tablets in the Netherlands, and its changes throughout the years. Moreover, the results were used for national and international risk assessments and important warning and prevention activities.

Sequential analysis of social play behavior in juvenile rats: effects of morphine

The effects of morphine on social play behavior in juvenile rats were investigated using sequential analysis. Social play behavior of 21-day-old rats treated with 1.0 mg/kg of morphine or saline was analyzed for 15 min. Frequencies and durations of measures of social play behavior, such as pinning, boxing/wrestling and following/chasing were significantly increased after treatment with morphine. Social behaviors not related to play, such as social exploration and crawling over/under were slightly decreased, while social grooming and non-social behavior were not affected by morphine treatment. Using sequential analysis, the dissociation between social behaviors related and unrelated to play was confirmed. Pinning and boxing/wrestling were highly significantly associated. In addition, crawling over/under significantly often preceded social grooming, and an association between social exploration and non-social behavior was found as well. Pinning and boxing/wrestling appeared to be negatively associated with non-social behaviors, social exploration and crawling over/under. A negative association between social grooming and social exploration was also found. Upon treatment with morphine, no major effects on the sequential structure of social behavior were observed: pinning and boxing/wrestling appeared more associated with following/chasing, and the negative association between pinning and boxing/wrestling on the one hand and social exploration on the other was enhanced. Thus, morphine slightly increased the coherence of social play behavior. It is concluded that morphine exerts its effects on social play behavior by increasing social play behavior as a whole rather than by changing its structure, suggesting a key role for opioid systems in the regulation of social play behavior.

Does Cannabidiol Protect Against Adverse Psychological Effects of THC

The recreational use of cannabis can have persistent adverse effects on mental health. Delta-9-tetrahydrocannabinol (THC) is the main psychoactive constituent of cannabis, and most, if not all, of the effects associated with the use of cannabis are caused by THC. Recent studies have suggested a possible protective effect of another cannabinoid, cannabidiol (CBD). A literature search was performed in the bibliographic databases PubMed, PsycINFO, and Web of Science using the keyword “cannabidiol.” After removing duplicate entries, 1295 unique titles remained. Based on the titles and abstracts, an initial selection was made. The reference lists of the publications identified in this manner were examined for additional references. Cannabis is not a safe drug. Depending on how often someone uses, the age of onset, the potency of the cannabis that is used and someone’s individual sensitivity, the recreational use of cannabis may cause permanent psychological disorders. Most recreational users will never be faced with such persistent mental illness, but in some individuals cannabis use leads to undesirable effects: cognitive impairment, anxiety, paranoia, and increased risks of developing chronic psychosis or drug addiction. Studies examining the protective effects of CBD have shown that CBD can counteract the negative effects of THC. However, the question remains of how the laboratory results translate to the types of cannabis that are encountered by real-world recreational users.

The Drug Information and Monitoring System (DIMS) in the Netherlands: Implementation, results, and international comparison

The Ministry of Health in the Netherlands has made illicit drug testing for drug users possible since the 1990s, in order to prevent serious health hazards associated with unexpected dangerous substances. This system of illicit drug testing is called the Drug Information and Monitoring System (DIMS). In nearly two decades, more than 100 000 drug samples have been handed in at DIMS testing facilities. This review describes the DIMS methodology and overviews results of the three main psychostimulant drug markets that have been monitored, i.e. ecstasy, amphetamine (speed), and cocaine. Additionally, monitoring results of hallucinogens are also described for the first time. For comparison, alternative international monitoring systems are described briefly alongside some of their results. Finally, drug monitoring is discussed from the perspectives of policy, prevention, and the drug users themselves.