Genetic Dissection of Behavioural and Autonomic Effects of Δ9-Tetrahydrocannabinol in Mice

Marijuana and its main psychotropic ingredient Δ⁹-tetrahydrocannabinol (THC) exert a plethora of psychoactive effects through the activation of the neuronal cannabinoid receptor type 1 (CB1), which is expressed by different neuronal subpopulations in the central nervous system. The exact neuroanatomical substrates underlying each effect of THC are, however, not known. We tested locomotor, hypothermic, analgesic, and cataleptic effects of THC in conditional knockout mouse lines, which lack the expression of CB1 in different neuronal subpopulations, including principal brain neurons, GABAergic neurons (those that release γ aminobutyric acid), cortical glutamatergic neurons, and neurons expressing the dopamine receptor D1, respectively. Surprisingly, mice lacking CB1 in GABAergic neurons responded to THC similarly as wild-type littermates did, whereas deletion of the receptor in all principal neurons abolished or strongly reduced the behavioural and autonomic responses to the drug. Moreover, locomotor and hypothermic effects of THC depend on cortical glutamatergic neurons, whereas the deletion of CB1 from the majority of striatal neurons and a subpopulation of cortical glutamatergic neurons blocked the cataleptic effect of the drug. These data show that several important pharmacological actions of THC do not depend on functional expression of CB1 on GABAergic interneurons, but on other neuronal populations, and pave the way to a refined interpretation of the pharmacological effects of cannabinoids on neuronal functions.     

Behavioural Syndromes,Partner Compatibility and Reproductive Performance in Steller’s Jays

The concept of partner compatibility in monogamous animals implies that individuals may reproduce better when paired to a partner with similar traits than to a higher quality, but dissimilar individual. We investigated whether partner similarities in traits that are linked in a behavioural syndrome influence reproductive performance in a wild population of Steller’s jays. In some years, pairs more similar in explorative tendencies and in willingness to take risks initiated nests earlier and were more likely to fledge offspring than dissimilar pairs. Benefits of behavioural similarity differed among breeding seasons, being most pronounced in a year with late breeding onset after a severe winter. Pairing patterns for behavioural traits also varied among years and traits, and assortative pairing of behaviourally similar partners was not only common overall, but was also correlated across the three explorative and risk‐taking tendencies. Pair members with behavioural similarities may yield more compatible and complementary partnerships. Our results indicate that compatibility across a suite of behavioural traits (i.e. a behavioural syndrome) may be beneficial for assortative pairs and support the hypothesis that the combination of traits in behavioural syndromes in itself might be a target for selection.     

Behavioural Syndromes in Urban and Rural Populations of Song Sparrows

Animals in urban habitats are often noticeably bold in the presence of humans. Such boldness may arise due to habituation, as urban animals learn, through repeated exposure, that passing humans do not represent a threat. However, there is growing research suggesting that: (1) inherent traits, as opposed to learned behaviour, influence which species invade urban habitats, and (2) individuals exhibit individual personality traits that limit behavioural flexibility, with the possible result that not all individuals would be able to demonstrate an appropriate level of boldness in urban environments. As a result, perhaps only birds with inherently bold personalities could successfully settle in an area of high human disturbance, and further, we might also expect to see the existence of behavioural syndromes, where boldness is correlated with variation in other behavioural traits such as aggression. In this study, we examined boldness and territorial aggression in urban and rural populations of song sparrows. We found that urban birds were bolder towards humans and that urban birds also showed higher levels of territorial aggression. We also found an overall correlation between boldness and territorial aggression, suggesting that urban boldness may be part of a behavioural syndrome. However, we see no correlation between boldness and aggression in the urban population, and thus, more work is needed to determine the mechanisms accounting for high levels of boldness and aggression urban song sparrows.     

Transporters – The View from Industry

The involvement of transport proteins in the disposition of drugs is receiving much attention of the scientific community. Recently, researchers from academia have surmised that drug transport rather than passive diffusion is the regular mechanism for molecules to cross cell membranes. On bare face value, however, sound evidence of the impact of transport proteins on clinical pharmacokinetics has been a trickle rather than a stream of convincing studies during the last decade, in stark contrast to the number of in vitro studies published. Progress in this area may have been impeded by a number of factors. Only a limited number of small‐molecule drugs fall within the physicochemical property space (i.e., high hydrophilicity and low passive permeability) that makes them predestined as transport protein substrates without other pharmacokinetic processes (e.g., passive diffusion, metabolism, nonspecific binding to tissue proteins) blurring the picture. The vast majority of drug molecules are lipophilic enough to be amenable to passive diffusion across cell membranes and to undergo metabolism to some extent. In these cases, clinical evidence relies heavily on the observation of pharmacokinetic drug–drug interactions not readily explained by the interference with drug metabolizing enzymes. Given the circumstances outlined above, it is not surprising that, based upon clinical observations, the final assessment as to the overall relevance of drug transport for clinical pharmacokinetics is still pending.     

Modelling of Nutrient Emissions in River Systems – MONERIS – Methods and Background

MONERIS is a semi‐empirical, conceptual model, which has gained international acceptance as a robust meso‐ to macro scale model for nutrient emissions. MONERIS is used to calculate nitrogen (N) and phosphorus (P) emissions into surface waters, in‐stream retention, and resulting loads, on a river catchment scale. This paper provides the first (i) comprehensive overview of the model structure (both the original elements and the new additions), (ii) depiction of the algorithms used for all pathways, and for retention in surface waters, and (iii) illustration of the monthly disaggregation of emissions and the implementation of measures. The model can be used for different climatic conditions, long term historical studies, and for future development scenarios. The minimum validated spatial resolution is 50 km², with a temporal resolution of yearly or monthly time steps. The model considers seven emission pathways (atmospheric deposition on surface waters, overland flow, erosion, tile drainage, groundwater, emissions from sealed urban areas, and point sources), and six emission sources (natural background, fertilizer application, nitrogen atmospheric deposition on arable land and other areas, urban sources, and point sources); and these are calculated separately for different land‐uses. The pathway and source‐related approach is a prerequisite for the implementation of measures to reduce non‐point and point‐source emissions. Therefore, we have modified MONERIS by the addition of a “management alternative” tool which can identify the potential effectiveness of nutrient reduction measures. MONERIS is an appropriate tool for addressing the scientific and political aspects of river basin management in support of a good surface water quality. (© 2011 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)