Hippocampal slice cannabinoid studies

The anecdotal reports of effects of smoking cannabis on cognitive processes has naturally prompted investigation into the effects of cannabinoids on synaptic plasticity, and in particular long-term potentiation (LTP). To summarise 17 years of effort, it has been easy to show that cannabinoids have effects on LTP, and most commonly suppress it, but far more difficult to define the mechanisms by which this occurs. Emerging themes are that the commonly reported inhibition of LTP by synthetic cannabinoids may be mediated by non-CBi receptors, and that the function of the endogenous cannabinoid system may be to facilitate induction of LTP. The vast majority of studies have focussed on synaptic plasticity in the CAI region of the rat hippocampal slice and we will start our review there. 

The range of putative endogenous cannabinoids have been outlined previously (see Di Marzo et al., this volume), and several studies have investigated the effects of application of fhese on LTP. In rat hippocampal slices, perfusion of 20 pM sn-2 arachidonylglycerol (2-AG) blocked LTP of CAl field EPSPs induced by high-frequency stimulation (100 Hz for 1 s), with lit tle or no effect on fhe baseline field... 

Activated CBi receptors can also change fhe function of several types of potassium channels. In oocytes and AtT20 cells artificially expressing the CBi receptor, stimulation of inwardly rectifying potassium channels was repeatedly observed (Henry and Chavkin 1995 Mackie et al. 1995 Garcia et al. 1998 McAllister et al. 1999). Potassium A currents in cultured hippocampal neurons are stimulated by cannabinoids (Deadwyler et al. 1995 Mu et al. 2000). The effects of cannabinoids on potassium M currents in hippocampal brain slices have also been studied M currents were inhibited, which means an enhancement of neuronal excitability (Schweitzer 2000). The potassium K current is inhibited by cannabinoids in cultured hippocampal neurons (Hampson et al. 2000). As in the case of calcium channels, anandamide can elicit a CBi receptor-independent effect on potassium... 

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