Benzodiazepine receptor ligand influences on learning: an endogenous modulatory mechanism mediated by benzodiazepines possibly of alimentary origin

Abstract

In rats, pre- but not post-training ip administration of either flumazenil, a central benzodiazepine (BZD) receptor antagonist, or of n-butyl-B-carboline-carboxylate (BCCB), an inverse agonist, enhanced retention of inhibitory avoidance learning. Flumazenil blocked the enhancing effect of BCCB, and the inhibitory effect of the BZD agonists clonazepam and diazepam also given pre-training. Post-training administration of these drugs had no effect. The peripheral BZD receptor agonist/chloride channel blocker Ro5-4864 had no effect on the inhibitory avoidance task when given ip prior to training, but it caused enhancement when given immediately post-training either ip or icv. This effect was blocked by PK11195, a competitive antagonist of Ro5-4864. These results suggest that there is an endogenous mechanism mediated by BZD agonists, which is sensitive to inverse agonists and that normally down-regulates the formation of memories through a mechanism involving GABA-A receptors and the corresponding chloride channels. The most likely agonists for the endogenous mechanism suggested are the diazepam-like BZDs found in brain whose origin is possibly alimentary. Levels of these BZDs in the cortex were found to sharply decrease after inhibitory avoidance training or mere exposure to the training apparatus.

A rodent model of appetitive discrimination with concomitant evaluation of anxiety-like behavior

“…On the other hand, in the first 5 min of the test session, the saline-treated group showed preference for the rewarded arm, indicating task retrieval, whereas DZP-treated animals explore both neutral and rewarded arms likewise, indicating a retention deficit. This result is in accordance with previous studies showing that anxiolytic drugs, particularly benzodiazepines, induce memory impairment (Scharf et al, 1984;Izquierdo et al, 1991Izquierdo et al, , 1992Izquierdo and Medina, 1997).…”

“…Indeed, it is believed that brain arousal is related to memory consolidation and anxiety, while brain inhibition underlies memory deficits and low anxiety levels (Kalueff, 2007). There is evidence that anxiolytic and anxiogenic drugs induce amnesia (Izquierdo et al, 1990(Izquierdo et al, , 1991(Izquierdo et al, , 1992Bates, 1996;Izquierdo and Medina, 1997) and improved memory (Izquierdo et al, 1990;Ribeiro et al, 1999), respectively. However, some studies have not corroborated these findings.…”

The effect of Coriandrum sativum seed extract on the learning of newborn mice by electric shock: interaction with caffeine and diazepam

“…It is well known that benzodiazepines have a negative effect on memory and have been used by anesthesiologists since in 1964 19. The suppressive effect of benzodiazepines on learning and memory, especially in the encoding stage, has been confirmed by investigations 20–22. In our study, mice in the group with coriander pretreatment that were given diazepam had the shortest average latency time; these changes were statistically significant.…”

Platelet‐activating factor induces permeability transition and cytochrome c release in isolated brain mitochondria

“…A likely candidate is PBR. This receptor is involved in the regulation of steroid synthesis (McCauley et al, 1995; Gavish et al, 1999), cell‐cycle control, learning and memory formation (Izquierdo et al, 1991a,b), peripheral nerve regeneration (Lacor et al, 1999), and in the mediation of the inflammatory response (Taupin et al, 1993; Torres et al, 2000) including platelet aggregation (Choppin and Berry, 1995). PBR consists of at least three subunits (Gavish et al, 1999) and is a component of the mitochondrial permeability pore (Snyder et al, 1987).…”