The Effects of Ethanol and Crocin on the Induction of Long-Term Potentiation in the CA1 Region of Rat Hippocampal Slices

Abstract

ABSTRACT-The effects of ethanol and crocin on the induction of long-term potentiation (LTP) were investigated in the CAI region of rat hippocampal slices in vitro. Ethanol (50-75 mM) suppressed the LTP induced by strong tetanic stimulation (51 pulses at 100 Hz). Crocin (20 rM) did not affect the baseline synaptic responses, but significantly prevented the LTP-suppressing action of ethanol. This effect of crocin was concentration dependent (10 -30 pM). Crocin (20 pM) alone did not affect the potentiation induced by weak tetanic stimulation (11 pulses at 100 Hz). These in vitro observations suggest that crocin directly prevents the LTP-suppressing action of ethanol within the hippocampus.Keywords: Crocin, Ethanol, Long-term potentiation *To whom correspondence should be addressed .The pistils of Crocus sativus L. are generally used in Chinese traditional medicine for anodyne, tranquid and emmenagogue, and its crude extract and purified chemicals have been demonstrated to prevent tumor formation, atherosclerosis or hepatic damages (1-4). Furthermore, it has been reported that oral administration of the ethanol extract of Crocus sativus L. (CSE) improves the ethanol-induced impairment of memory acquisition of mice in passive avoidance tasks (5), suggesting that CSE has an ameliorating effect on ethanol-induced impairment of learning and memory.The synapses of the hippocampus display a long-lasting increase in strength of synaptic communication following high-frequency stimulation of afferents. This phenomenon is termed long-term potentiation (LTP), and it is believed to be the cellular basis of learning and memory (6). To elucidate the mechanisms underlying the memory-improving action of CSE, we have previously investigated the in vivo effects of CSE and crocin, a major constituent of CSE (7), on hippocampal LTP by using anesthetized rats. Ethanol suppressed the induction of LTP, but when CSE was administered prior to ethanol, hippocampal LTP was normally induced (8). Similarly, intracerebroventricular injection of crocin prevented the LTP-suppressing effect of ethanol (9). These observations suggest that CSE improves the memory function by preventing the LTP-suppressing action of ethanol and that crocin is responsible for this biological activity.Since our previous studies were conducted in vivo with anesthetized rats, it remained unclear whether or not crocin interacts with ethanol within the hippocampus. To resolve this issue, in the present study, we investigated the effects of ethanol and crocin on the induction of LTP in the CAI region of rat hippocampal slices in vitro.Crocin was purified from CSE as described in our previous paper (9). The chemical structure of crocin is shown in Fig. 1. The hippocampal slice preparation and recording of evoked potentials were made as described in our previous paper (10). Briefly, hippocampal slices (400-500 tam) were quickly prepared from male Wistar rats (8-to 9-weeks-old) and maintained in a chamber at 35°C, where they were continuously perfused with artificial cerebrospi...

Prenatal Ethanol (EtOH) Exposure Alters the Sensitivity of the Adult Dentate Gyrus to Acute EtOH Exposure

“…Additionally, we showed that LTP was attenuated following the application of both moderate (20 mM) and high (50 mM) levels of EtOH. Accordingly, the gradual decrease in the magnitude of LTP as the result of an increase in EtOH concentration has been reported by several groups in the CA1 (Izumi et al, 2007;Lovinger et al, 1990;Sugiura et al, 1995).…”

Modulation of hippocampal long-term potentiation by slow increases in ethanol concentration

“…The concentration of ethanol required for LTP inhibition, however, has varied widely among reports. While many studies have found that ethanol inhibits LTP induction at concentrations of 50 mM or more (Randall et al, 1995;Sugiura et al, 1995;Schummers et al, 1997), some reports have shown that concentrations as low as 5 mM also impair LTP induction (Blitzer et al, 1990). The inconsistencies in these studies may reflect experimental differences including slice Correspondence: Yukitoshi Izumi, M.D., Ph.D., Department of Psychiatry, Washington University School of Medicine, 660 South Euclid, Box 8134, St. Louis, MO 63110, USA, Phone: +1 314 362 8659, Fax: +1 314 747 2983, Email: izumiy@psychiatry.wustl.edu Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication.…”

The ethanol metabolite acetaldehyde inhibits the induction of long‐term potentiation in the rat dentate gyrus in vivo

“…This phenomenon is termed long‐term potentiation (LTP), and is widely believed to be part of the cellular basis of learning and memory. As a plausible explanation for ethanol‐induced memory impairments, several groups have reported that ethanol inhibits the induction of LTP in hippocampal slices in vitro ( Sinclair & Lo, 1986 ; Blitzer et al ., 1990 ; Morrisett & Swartzwelder, 1993 ; Sugiura et al ., 1995 ). However, two questions remained to be solved.…”