Immunocytochemistry using an antiserum to the C-terminal octapeptide of synenkephalin, proenkephalin(63-70), was performed throughout the rat brain and revealed numerous immunopositive fibers and some cell bodies. The morphology and distribution of synenkephalin immunoreactivity was extremely similar to that of a commercial methionine enkephalin (Met-ENK) antiserum. Colchicine pretreatment allowed the immunostaining of cell bodies not otherwise possible without pretreatment, but did not affect the distribution of immunoreactive fibers. Using 6 microns serial sections, we were able to colocalize synenkephalin and Met-ENK immunoreactivities in gigantocellular neurons of the medullary reticular formation. Preabsorption of the antiserum with [Tyr63]proenkephalin(63-70) octapeptide (YEESHLLA) completely eliminated immunoreactivity in the rat brain, while preabsorption with all other peptides used had no detectable effect. We conclude that our antiserum to synenkephalin is specific for enkephalinergic cell bodies, fibers and terminals. The synenkephalin antiserum used in these studies may have advantages over other antisera utilized for immunocytochemical detection of proenkephalin gene expression.

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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.

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PubMedDate not supplied

Effects of convulsant ligands of the GABA-benzodiazepine receptor complex in conflict and learning tasks in mice.

A systematic study of the effects of convulsants acting at the GABA-benzodiazepine receptor complex was undertaken in mice to estimate their potential anxiogenic effects and/or performance enhancing effects in learning and memory tasks. Anxiogenic effects were assessed in a conflict task where lever presses delivered both a food pellet and a mild electric foot shock. Effects on learning were assessed through analysis of habituation to a new environment. The convulsant agents pentylenetetrazol (PTZ) and picrotoxin (PX), both acting through the GABA-benzodiazepine receptor complex, and strychnine, a convulsant acting through the glycine transmission were used. Our data show that non convulsive doses of PTZ (25 mg/kg) and PX (0.85 mg/kg), but not of strychnine (0.8 mg/kg), are anxiogenic in the conflict model. At lower doses PTZ (10 mg/kg) and PX (0.3 mg/kg), but not strychnine (0.1 to 0.6 mg/kg), enhance performance in the habituation model. Our results contribute to the validation of the idea that small decreases in GABAergic transmission are accompanied by improvement of learning whereas medium decreases induce anxiogenic effects.

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