Globus pallidus neurons receive GABAergic input from the caudate-putamen via the striatopallidal pathway. Anatomical studies indicate that many CB 1 cannabinoid receptors are localized on terminals of striatopallidal axons. Accordingly, the hypothesis of the present work was that activation of CB 1 receptors presynaptically inhibits neurotransmission between striatopallidal axons and globus pallidus neurons. In sagittal mouse brain slices, striatopallidal axons were electrically stimulated in the caudate-putamen, and the resulting GABAergic inhibitory postsynaptic currents (IPSCs) were recorded in globus pallidus neurons. The synthetic cannabinoid receptor agonists R(ϩ)- [2,3-dihydro-5-methyl-3-[(morpholinyl) Prevention of DSI by rimonabant indicates that endocannabinoids released from the postsynaptic neurons acted on CB 1 receptors to suppress synaptic transmission. WIN55212-2 did not modify currents in globus pallidus neurons elicited by GABA released from its chemically bound ("caged") form by a flash pulse, suggesting that WIN55212-2 depressed neurotransmission presynaptically. For studying the mechanism of the inhibition of GABA release, terminals of striatopallidal axons were labeled with a calcium-sensitive fluorescent dye. WIN55212-2 depressed the action potentialevoked increase in axon terminal calcium concentration. The results show that activation of CB 1 receptors by exogenous and endogenous cannabinoids leads to presynaptic inhibition of neurotransmission between striatopallidal axons and globus pallidus neurons. Depression of the action potential-evoked calcium influx into axon terminals is the probable mechanism of this inhibition.The G␣ i/o protein-coupled CB 1 cannabinoid receptor is the primary neuronal target of the phytocannabinoid ⌬ 9 -tetrahydrocannabinol and of the endogenous cannabinoids (endocannabinoids) anandamide and 2-arachidonylglycerol (Howlett et al., 2002;Abood, 2005). The CB 1 receptor is widely distributed in the central and the peripheral nervous system (Herkenham et al., 1991b;Mailleux and Vanderhaeghen, 1992;Tsou et al., 1998). Activation of CB 1 receptors leads to presynaptic inhibition of synaptic transmission in many regions of the central and peripheral nervous system (Freund et al., 2003;Szabo and Schlicker, 2005).The present work focuses on the neuronal connection between the caudate putamen and the globus pallidus (also called external or lateral globus pallidus). Globus pallidus neurons receive strong GABAergic input from medium spiny neurons of the caudate-putamen (striatopallidal projection neurons; Gerfen, 2004). The concentration of CB 1 receptor protein in the globus pallidus is very high (Herkenham et al., 1991b;Mailleux and Vanderhaeghen, 1992;Tsou et al., 1998). Two kinds of observations support the idea that the majority of CB 1 receptors in the globus pallidus is localized This work was supported by the Deutsche Forschungsgemeinschaft (Sz 72/5-1).Article, publication date, and citation information can be found at

Silent hypoglycemia tended to occur more often and to last longer in patients with HbA1c <7%. However, patients with HbA1c >7% had a higher glycemic variability. HbA1c >7% wasn't a reliable indicator of lower risk of hypoglycemia.

In England, chlamydia positivity in young men occurs at a slightly older age group (20-24 years) than positivity among young women (16-20 years) but total rates of infection among the population aged under 25 years are similar. Where there is variation, explanations often focus on individual sexual risk behaviours. We aimed to explore the extent to which variations in chlamydia positivity could be explained by reasons for attendance and sexual behaviour at a sexual health clinic in a high-prevalence area of England. Data routinely collected during clinic appointments were extracted retrospectively from the medical records of 952 clinic users (634 women) aged 16 to 24. We tested for associations with chlamydia positivity using the Chi square statistic and multiple logistic regression for men and women separately; 19.5% of men tested positive (95% CI: 15.1-23.8) compared to 11.5% of women (95% CI: 9.0-14.0). Reporting a partner with symptoms or a sexually transmitted infection diagnosis was significantly associated with a positive diagnosis (Men OR: 3.14, 95% CI: 1.5-6.25; Women OR: 3.78, 95% CI: 1.83-7.83). All other reasons for attendance and all sexual behaviour variables were not significantly associated with a positive diagnosis. Differences in chlamydia positivity between men and women attending this service cannot be explained by individual sexual behaviours found to be associated with higher risk of infection in national studies. Our findings question the utility of individual behavioural data routinely collected during clinic appointments for predicting risk of sexually transmitted infections in high-prevalence areas.

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