Behavioural Brain Research 142 (2003) 31–40 Research report Role of platelet activating factor in triazolobenzodiazepines-induced retrograde amnesia Manish Kumar Saraf, Kamal Kishore, Koshi M. Thomas, Ajay Sharma, Manjeet Singh ∗ Department of Pharmaceutical Sciences and Drug Research, Punjabi University, Patiala 147002, Punjab, India Received 26 June 2002; received in revised form 21 October 2002; accepted 21 October 2002 Abstract Benzodiazepine (diazepam), triazolobenzodiazepines (brotizolam, triazolam) and platelet activating factor (PAF) antagonist (BN 52021) are administered to mice before acquisition and retrieval trials conducted using Morris water maze. Benzodiazepine has produced only anterograde amnesia and it has not produced retrograde amnesia. Triazolobenzodiazepines have produced both anterograde and retrograde amnesia. PAF antagonist (BN 52021) has only produced retrograde amnesia and it has not produced anterograde amnesia. The anterograde amnesia produced by benzodiazepine and triazolobenzodiazepines, has been prevented by benzodiazepine receptor antagonist (flumazenil). It suggests that benzodiazepine- and triazolobenzodiazepines-induced anterograde amnesia may be mediated through benzodiazepine receptors. On the other hand, retrograde amnesia produced by PAF antagonist (BN 52021) and triazolobenzodiazepines has been attenuated by PAF and PAF acetyl hydrolase inhibitors such as cigarette smoke extract (CSE) and phenylmethanesulfonylflouride. It suggests that triazolobenzodiazepine-induced retrograde amnesia may be mediated through blockade of PAF receptors. © 2002 Published by Elsevier Science B.V. Keywords: Amnesia; Benzodiazepine receptor; BN 52021; PAF receptor; PMSF; Triazolobenzodiazepine 1. Introduction Anterograde amnesia is an impairment to store new memories [19,21,26] and retrograde amnesia is a failure to retrieve old memories [19,34]. Activation of benzodi- azepine receptors is reported to produce anterograde amne- sia [20,28]. Benzodiazepine receptor antagonists such as a flumazenil [31], CGS 8216 [3] and benzodiazepine receptor inverse agonists such as beta-carbolines [11,39] are noted to attenuate benzodiazepine-induced anterograde amnesia. Al- prazolam, a triazolobenzodiazepine is reported to produce both anterograde and retrograde amnesia and flumazenil is noted to attenuate alprazolam-induced anterograde amnesia [33]. Platelet activating factor (PAF) is 1-O-alkyl-2-acetyl-sn- glycero-3-phosphocholine. The existence of PAF [24,36] and its binding sites [36] in brain is well documented. High frequency stimulation of presynaptic neurons has been re- ported to increase the release of PAF and produce long-term ∗ Corresponding author. Tel.: +91-175-2282461x6184; fax: +91-175-2283073/2282437. E-mail address: manjeet@pbi.ernet.in (M. Singh). potentiation (LTP) [16]. The application of PAF antagonists such as BN 52021 to CA1 neurons of the hippocampus has prevented brief tetanus-induced LTP [2,15,16]. Moreover, administration of PAF antagonists to the hippocampus or amygdala has been reported to produce amnesia [13]. BN 50730, a PAF receptor antagonist, has been reported to pro- duce retrograde amnesia [32,33]. Triazolobenzodiazepines act as benzodiazepine receptor agonists [14,17,22,35] and are also noted to block PAF receptors [4–6]. Therefore, the present study has been de- signed to investigate the role of PAF in triazolobenzo- diazepine-induced amnesia. 2. Material and methods Swiss albino mice (20–40 g) of either sex were used in the present study. They were exposed to 12h light and dark cycle and had free access to water and standard diet (Kisan Feeds Ltd., Mumbai, India). The experiments were conducted between 10.00 and 17.30 h in a semi sound- proof laboratory and were in accordance with guidelines of institutional animal ethics committee. 0166-4328/02/$ – see front matter © 2002 Published by Elsevier Science B.V. doi:10.1016/S0166-4328(02)00365-0