Drugs and their effects on olfactory learning processes in rats were tested using a modified version of the runway apparatus developed by Ades. Rats were first exposed to a conspecific urine sample and 24 h later were exposed to the same stimulus in the runway. Observations recorded the time spent investigating the urine and the number of sniffs at the site, these being considered to be indices of memory. Diazepam-treated rats (4 or 6 mg/kg) and scopolamine-treated rats (0.5 or 1 mg/kg) showed increases for both parameters. When both drugs were administered simultaneously, the impairing effect was potentiated. However, no changes in learning responses were observed in rats treated with physostigmine (0.125, 0.25, 0.5 mg/kg) or methyl beta-carboline-3-carboxylate (0.3, 0.5, 1 mg/kg), although the administration of physostigmine or methyl beta-carboline-3-carboxylate was shown to antagonize the impairing effect of diazepam or scopolamine respectively. These observations support the hypothesis of interactions existing between cholinergic agents and benzodiazepine receptor ligands and of such interactions affecting olfactory acquisition processes. The runway apparatus appears to be a valid candidate model to be used for the assessment of pharmacological influences on olfactory learning in rats.

Animals↗

PubMedDate not supplied

Benzodiazepine impairs and beta-carboline enhances performance in learning and memory tasks.

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.

Animals↗

PubMedDate not supplied

Mouse chromosomes 4 and 13 are involved in beta-carboline-induced seizures.

beta-Carbolines, such as methyl beta-carboline-3-carboxylate (beta-CCM), attach to the benzodiazepine receptors in the brain, but have effects completely opposite to those of benzodiazepines: beta-CCM is a convulsant at high doses, an anxiogenic at moderate doses, and enhances learning at low doses. The aim of this work was to detect some of the chromosomal segments involved in the regulation of beta-CCM-induced seizures. The method used was a derivation of the classical use of linkage-testing strains. We tested several strains and some of their intercrosses and back-crosses. For two of these strains, we obtained significant results showing that genes located on chromosomes 4 and 13, provisionally termed respectively Bis1 and Bis2, were involved in the regulation of beta-carboline-induced seizures. Testing of these two strains with two other convulsant agents (pentylenetetrazol, which acts at the picrotoxine site of the GABA receptor complex, and strychnine, which acts at the glycinergic receptor) provided evidence that the genes implicated are not involved in general seizure processes but specifically in beta-CCM-induced seizures.

Animals↗

PubMedDate not supplied

Analysis of B10.D2 recombinant congenic mouse strains shows that audiogenic and beta-CCM-induced seizures depend on different genetic mechanisms.

The rate of occurrence of audiogenic seizures and seizures induced by the benzodiazepine receptor inverse agonist methyl-beta-carboline-3-carboxylate (beta-CCM) were analyzed in several recombinant congenic strains of mice bred from B10.D2 and DBA/2J. Although both types of seizures have similar behavioral patterns and might involve GABAergic mechanisms, no correlation was observed between the occurrence of the two types of seizures across the strains, suggesting that these two types of seizures depend on different genetic mechanisms.

Acoustic Stimulation↗