The transient receptor potential vanilloid type 1 (TRPV1) channel is a well recognized polymodal signal detector that is activated by painful stimuli such as capsaicin. Here, we show that TRPV1 is expressed in the lateral nucleus of the amygdala (LA). Despite the fact that the central amygdala displays the highest neuronal density, the highest density of TRPV1 labeled neurons was found within the nuclei of the basolateral complex of the amygdala. Capsaicin specifically changed the magnitude of long-term potentiation (LTP) in the LA in brain slices of mice depending on the anesthetic (ether, isoflurane) used before euthanasia. After ether anesthesia, capsaicin had a suppressive effect on LA-LTP both in patch clamp and in extracellular recordings. The capsaicin-induced reduction of LTP was completely blocked by the nitric oxide synthase (NOS) inhibitor L-NAME and was absent in neuronal NOS as well as in TRPV1 deficient mice. The specific antagonist of cannabinoid receptor type 1 (CB1), AM 251, was also able to reduce the inhibitory effect of capsaicin on LA-LTP, suggesting that stimulation of TRPV1 provokes the generation of anandamide in the brain which seems to inhibit NO synthesis. After isoflurane anesthesia before euthanasia capsaicin caused a TRPV1-mediated increase in the magnitude of LA-LTP. Therefore, our results also indicate that the appropriate choice of the anesthetics used is an important consideration when brain plasticity and the action of endovanilloids will be evaluated. In summary, our results demonstrate that TRPV1 may be involved in the amygdala control of learning mechanisms.

Background and Purpose Gamma oscillations are fast rhythmic fluctuations of neuronal network activity ranging from 30 to 90 Hz that establish a precise temporal background for cognitive processes such as perception, sensory processing, learning, and memory. Alterations of gamma oscillations have been observed in schizophrenia and are suggested to play crucial roles in the generation of positive, negative, and cognitive symptoms of the disease. Experimental Approach In this study, we investigated the effects of the novel antipsychotic cariprazine, a D3‐preferring dopamine D3/D2 receptor partial agonist, on cholinergically induced gamma oscillations in rat hippocampal slices from treatment‐naïve and MK‐801‐treated rats, a model of acute first‐episode schizophrenia. Key Results The D3 receptor‐preferring agonist pramipexole effectively decreased the power of gamma oscillations, while the D3 receptor antagonist SB‐277011 had no effect. In treatment‐naïve animals, cariprazine did not modulate strong gamma oscillations but slightly improved the periodicity of non‐saturated gamma activity. Cariprazine showed a clear partial agonistic profile at D3 receptors at the network level by potentiating the inhibitory effects when the D3 receptor tone was low and antagonizing the effects when the tone was high. In hippocampal slices of MK‐801‐treated rats, cariprazine allowed stabilization of the aberrant increase in gamma oscillation power and potentiated resynchronization of the oscillations. Conclusion and Implications Data from this study indicate that cariprazine stabilizes pathological hippocampal gamma oscillations, presumably by its partial agonistic profile. The results demonstrate in vitro gamma oscillations as predictive biomarkers to study the effects of antipsychotics preclinically at the network level.

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Background: The amygdala receives afferent sensory input and processes information related to hydromineral balance. Angiotensin acts on and through the amygdala to stimulate thirst and sodium appetite. In addition, different angiotensins seem to play a role in cognition and learning mechanisms by acting on and through the amygdala. Recently, we showed that angiotensin-(1–7) (Ang-(1–7)) enhances the magnitude of long-term potentiation (LTP) in the lateral nucleus of the amygdala (LA) via the Mas receptor. Methods: Extracellular field potentials were measured in the LA. Results: LA-LTP induced by stimulation of the external capsule was nitric oxide (NO)-dependent because the NO synthase (NOS) inhibitor L-NAME reduced LA-LTP. The LA-LTP was also reduced in both male and female nNOS and eNOS knockout mice. In male eNOS^–/– mice, Ang-(1–7) enhanced LA-LTP, whereas the LTP-enhancing effect of Ang-(1–7) was missing in female eNOS^–/– mice. Therefore, the LTP-enhancing effect of Ang-(1–7) was mediated by eNOS in females. In contrast, Ang-(1–7) strongly enhanced the LTP in nNOS^–/– females, whereas the effect of Ang-(1–7) was missing in nNOS^–/– males. Thus, Ang-(1–7) induced an increase in the magnitude of LTP via the involvement of nNOS in males. Conclusion: Our data support not only the hypothesis that NO contributes to plasticity changes in the lateral amygdala, but also show for the first time a gender-dependent involvement of different isoforms of NOS in the mediation of Ang-(1–7) on LTP in the amygdala.