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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

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