Elisabetta Baldi

Several psychiatric conditions such as phobias, generalized anxiety, and post-traumatic stress disorder (PTSD) are characterized by pathological fear and anxiety. The main therapeutic approach used in the management of these disorders is exposure-based therapy, which is conceptually based upon fear extinction with the formation of a new safe memory association, allowing the reduction in behavioral conditioned fear responses. Nevertheless, this approach is only partially resolutive, since many patients have difficulty following the demanding and long process, and relapses are frequently observed over time. One strategy to improve the efficacy of the cognitive therapy is the combination with pharmacological agents. Therefore, the identification of compounds able to strengthen the formation and persistence of the inhibitory associations is a key goal. Recently, growing interest has been aroused by the neuropeptide oxytocin (OXT), which has been shown to have anxiolytic effects. Furthermore, OXT receptors and binding sites have been found in the critical brain structures involved in fear extinction. In this review, the recent literature addressing the complex effects of OXT on fear extinction at preclinical and clinical levels is discussed. These studies suggest that the OXT roles in fear behavior are due to its local effects in several brain regions, most notably, distinct amygdaloid regions.

The role of the perirhinal cortex (PC) in conditioned taste aversion (CTA) learning was investigated in Long Evans rats. CTA was induced by the intraperitoneal administration of LiCl 60 min after saccharin-sweetened water drinking. The PC was reversibly inactivated by the stereotaxic administration of tetrodotoxin (TTX) 60 min before saccharin drinking, immediately after saccharin drinking (Experiment 1), 6 or 24 hr after LiCl administration (Experiment 2), and 60 min before CTA retrieval testing (Experiment 3). Only pre-saccharin drinking PC inactivation disrupted CTA. Thus, PC integrity is necessary only during the earliest phases of CTA mnemonic processing, that is, taste information acquisition and early gustatory memory elaboration. The results are discussed in relation to PC connectivity and PC temporal involvement in the memorization process of other aversive responses.

By means of the fully reversible tetrodotoxin inactivation technique, perirhinal cortex (PC) mnemonic function was investigated in rats trained to a passive avoidance response (PAR). It was shown that PC functional integrity is necessary during PAR acquisition, during late and very late consolidation (from 24 hr up to 192 hr after the training session), and during retrieval. An unexpected finding was that the PC was not involved in the early consolidation period. Thus the PC may play a relatively simple relay or connective role during acquisition, but its very late and very long consolidative involvement may indicate a peculiar function in consolidation and possibly in the storage of the PAR engram. The results are discussed in terms of the mnemonic characteristics of other neural sites (amygdala, hippocampus, and entorhinal cortex) involved in the same learning process.