Book of abstracts - British Neuroscience Association
Book of abstracts - British Neuroscience Association
Book of abstracts - British Neuroscience Association
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20.01<br />
Cannabinoid neuropharmacology: recent developments<br />
Ross R<br />
Institute <strong>of</strong> Medical Sciences, University <strong>of</strong> Aberdeen. Aberdeen. AB25<br />
2ZD. Scotland.<br />
The endocannabinoid system comprises two known receptors (CB1<br />
and CB2); a family <strong>of</strong> endogenous ligands; and specific molecular<br />
machinery for the synthesis, transport, and inactivation <strong>of</strong> CB ligands.<br />
CB1 receptors are highly expressed throughout the CNS and, more<br />
recently, CB2 receptors have been identified and functionally<br />
characterised in the brainstem; however, CB2 receptor expression on<br />
neurones remains the subject <strong>of</strong> controversy. There is considerable<br />
pharmacological evidence that the endocannabinoid system may<br />
encompass additional targets. For example, recent patent applications<br />
provide the first evidence that certain synthetic and endogenous<br />
cannabinoids interact with orphan receptors, a prominent example<br />
being GPR55. Evidence has also emerged that the cannabinoid CB1<br />
receptor contains an allosteric binding site. Novel compounds<br />
targeting this site thereby herald a new generation <strong>of</strong> therapeutics to<br />
be used, for example, as analgesics (allosteric enhancers) or antiobesity<br />
agents (allosteric inhibitors). The endocannabinoids,<br />
anandamide and 2-arachidonoylglycerol (2-AG) are rapidly hydrolysed<br />
by the microsomal enzyme, fatty acid amide hydrolase (FAAH). They<br />
can also be metabolized by a range <strong>of</strong> oxygenase enzymes that are<br />
already known to convert arachidonic acid to potent biologically active<br />
compounds. These include cyclooxygenase, lipoxygenase and P450<br />
enzymes. Inhibition <strong>of</strong> COX-2 potentiates retrograde endocannabinoid<br />
effects in the hippocampus and PGE2 glycerol ester, a COX-2<br />
oxidative metabolite <strong>of</strong> 2-AG, modulates inhibitory synaptic<br />
transmission in hippocampal neurones. Oxygenation <strong>of</strong> anandamide<br />
and 2-AG may therefore lead to the production <strong>of</strong> a range <strong>of</strong> novel lipid<br />
products that may have an important physiological or<br />
pathophysiological role.<br />
20.02<br />
Influence <strong>of</strong> cannabinoids on neural fate<br />
Campbell V, Gowran A, Downer E<br />
Department <strong>of</strong> Physiology and Trinity College Institute <strong>of</strong> <strong>Neuroscience</strong>,<br />
Trinity College, Dublin 2, Ireland<br />
The cannabinoid system has been demonstrated to exert an influence on<br />
neuronal viability with neuroprotective and neurotoxic properties being<br />
reported. The neuroprotective effects are mediated through antioxidant<br />
properties whilst we have found that the neurotoxic effects are mediated<br />
through activation <strong>of</strong> the CB1 cannabinoid receptor, induction <strong>of</strong> stressactivated<br />
protein kinases and subsequent commitment to apoptosis.<br />
Exposure <strong>of</strong> cultured cortical neurons to tetrahydrocannabinol (THC, ЧM),<br />
the principal psychoactive moeity <strong>of</strong> marijuana, evokes apoptosis (P