LTP-blocking effect

Fig. (3). Effects of crocin and its analogues on the LTP-blocking effect of ethanol.

A Time-course of potentiation of population spike amplitude. Saline (, 0) or CSE (250 mg/kg, A ) was orally administered 30 min before tetanus, and then saline ( ) or 30% ethanol (O.A ) was orally administered 10 min later (20 min prior to tetanus). B The dose-dependency of the influence of CSE on the LTP-blocking effect of ethanol. The numbers of observations are as follows saline alone (control), n=9 ethanol alone, n=8 ethanol and 125 mg/kg CSE, n=5 ethanol and 250 mg/kg CSE, n=ll. All data are represented mean SEM of n observations. p<0.0l vs. saline group (control). p<0.01 vs. ethanol alone (Duncan s multiple range test). 

When 30 % of ethanol (20 ml/kg) was administrated by the intravenous injection 10 min prior to tetanus blocked the induction of LTP. By the oral CSE (125 and 250 mg/kg) administrations 20 min prior to ethanol injection, the LTP-blocking effect of intravenously injected ethanol was significantly attenuated dose-dependently Fig. (8-A). Fig. (8-B) indicated the dose-dependency of the influence of CSE on the LTP-blocking effect of ethanol. The effect of CSE was also observed when ethanol was injected intracerebroventricularly [13],... 

We already indicated that intravenous injection of ethanol blocked the LTP induced by tetanic stimulation [18]. However, when saffron crude extracts were injected intracerebroventricularly, the blocking effect of ethanol on the LTP decreased dose-dependently [19]. Moreover, crocin prevents the ethanol-induced impairment of memory acquisition in ST and SD tests [20], From these results it is easily suggested that crocin antagonized the blocking effect of ethanol on the induction of LTP. 

An oral administration of crocin had no effect on memory acquisition in normal mice but improved the ethanol-induced impairment of learning behaviors of mice in passive avoidance performance tasks. This phenomenon resembled that of crude extract of saffron as reported previously. The tendencies of the effect between CSE and crocin are similar to each other. From these results it can be easily speculated that crocin is the most important principle in crude extract of saffron. Other crocetin glucoside esters weakly antagonized the blocking effect of ethanol on the LTP compared to crocin. 

Crocin of 50 mg/kg ameliorated the blocking effect of ethanol on the LTP at approximately 84% compared to the control as indicated in Fig. (10). Crocetin gentiobiose glucose ester also antagonized the blocking effect of ethanol on the LTP dose-dependently. But die intensity is not so strong, about a half of crocin when compared the intensity of 50 mg/kg. On the other hand, crocetin di-glucose ester did not remove the inhibitory effect of ethanol on the LTP. 

Interest in the PGs has recently reverted to their precursor arachidonic acid (AA), which seems to be able to act intracellulary as a second messenger, and also extra-cellularly. In this latter mode it may play a part in LTP. It is known that AA produces a long-lasting enhancement of synaptic transmission in the hippocampus that resembles LTP and in fact activation of NMDA receptors leads to the release of AA by phospholipase A2 (see Dumuis et al. 1988) and inhibition of this enzyme prevents the induction of LTP. AA has also been shown to block the uptake of glutamate (see Williams and Bliss 1989) which would potentiate its effects on NMDA receptors. This would not only prolong LTP but also cause neurotoxicity. 

One of the cardinal features of a receptor-mediated effect is stereoselectivity. It was therefore significant that cannabinoids were shown to be stereoselective as inhibitors of LTP. HU-210 and HU-211 were the first to be tested, since their stereochemical purity is particularly high, and only HU-210 is psychoactive. The experiments by Collins et al. (1994) showed that pre-incubation of adult rat hippocampal slices with 100 nM HU-210, but not HU-211, blocked LTP of the CAI field excitatory postsynaptic potential (fEPSP) induced by high-frequency stimulation (100 Hz for 500 ms). Slices were pre-incubated with the drugs so there was... 

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... 

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