Benzodiazepine impairs and β-carboline enhances performance in learning and memory tasks

Abstract

Benzodiazepines are widely used anxiolytics and anticonvulsants, and their potent sedative properties are routinely used in presurgical anaesthesia. However, they are also known to induce a strong anterograde amnesia in patients. Specific benzodiazepine antagonists have recently been described, some of which have intrinsic pharmacological properties that are opposite to those of benzodiazepines. These have been called inverse agonists and they have been shown to be proconvulsant or convulsant whereas benzodiazepines are anticonvulsants. Inverse agonists are also anxiogenic rather than anxiolytic. Since benzodiazepines induce anterograde amnesia, we have investigated the possibility that inverse agonists might also have an opposite effect for this property and so enhance acquisition (learning) and (or) retention (memory). We report here that, in three different animal models, an inverse agonist of the beta-carboline group, methyl beta-carboline-3-carboxylate (beta-CCM), enhances animal performance in three different tasks used to investigate learning and memory.

Tiagabine Synergistically Interacts with Gabapentin in the Electroconvulsive Threshold Test in Mice

“…Time at which mice enter the dark box, was noted and subsequently, the medians with 25 and 75 percentiles were calculated. The step-through, dark-light passive avoidance task gives information about acquisition (learning), consolidation, and retrieval; therefore, may be regarded as a measure of long-term memory (Venault et al, 1986). The influence of AEDs administered alone or in combinations on long-term memory was evaluated in three variants as follows:…”

Disruptive Effect of Midazolam on Fear Memory Reconsolidation: Decisive Influence of Reactivation Time Span and Memory Age

“…Previous findings showed that allosteric modulators of g-amino butyric acid-A (GABA-A) receptors such as BDZ agents (positive modulators) or inverse agonist (negative modulators) of BDZ sites are effective in affecting these processes. BDZ compounds induce anxiolysis, sedation, and muscle relaxation (Thiebot, 1985;Venault et al, 1986;McNamara and Skelton, 1991;McNamara et al, 1993) and, under certain conditions, produce amnesia. Data derived from humans (Beracochea, 2006) and from laboratory animals have all shown that BDZ agents can impair memory.…”

Pharmacological and Behavioral Characteristics of Interactions between Vigabatrin and Conventional Antiepileptic Drugs in Pentylenetetrazole-Induced Seizures in Mice: An Isobolographic Analysis

“…The test was performed as described by Venault et al (1986). The apparatus consisted of a two-compartment chamber with an illuminated box (10 Â 13 Â 15 cm) connected to a large darkened box (25 Â 20 Â 15) by a guillotine door.…”

“…Time at which the mice entered the dark box was noted and subsequently, the medians with 25 and 75 percentiles were calculated. The step-through passive avoidance task gives information about ability to acquire the task (learning) and to recall the task (retrieval); therefore, may be regarded as a measure of long-term memory (Venault et al, 1986). The animals were administered with AEDs either singly or in combinations on the first day before training.…”

“…(1) Standard variantFperformed as described above in which the time duration of an electric footshock was constant for all groups of animals tested and established on a standard value of 2 s (Venault et al, 1986). (2) Modified variantFidentically performed as the standard variant except for the time duration of an electric footshock, which was based upon the median latency to the first pain reaction of animals subjected to the pain threshold test.…”