The role of serotonin (5-hydroxytryptamine [5-HT]) and 5-HT2A receptors in anxiety has been extensively studied, mostly without considering individual differences in trait anxiety. Our laboratory developed two lines of animals that are bred for high and low freezing responses to contextual cues that are previously associated with footshock (Carioca High-conditioned Freezing [CHF] and Carioca Low-conditioned Freezing [CLF]). The present study investigated whether ketanserin, a preferential 5-HT2A receptor blocker, exerts distinct anxiety-like profiles in these two lines of animals. In the first experiment, the animals received a systemic injection of ketanserin and were exposed to the elevated plus maze (EPM). In the second experiment, these two lines of animals received microinjections of ketanserin in the infralimbic (IL) and prelimbic (PL) cortices and were exposed to either the EPM or a contextual fear conditioning paradigm. The two rat lines exhibited bidirectional effects on anxiety-like behavior in the EPM and opposite responses to ketanserin. Both systemic and intra-IL cortex injections of ketanserin exerted anxiolytic-like effects in CHF rats but anxiogenic-like effects in CLF rats. Microinjections of ketanserin in the PL cortex also exerted anxiolytic-like effects in CHF rats but had no effect in CLF rats. These results suggest that the behavioral effects of 5-HT2A receptor antagonism might depend on genetic variability associated with baseline reactions to threatening situations and 5-HT2A receptor expression in the IL and PL cortices.Highlights CHF and CLF rats are two bidirectional lines that are based on contextual fear conditioning.CHF rats have a more “anxious” phenotype than CLF rats in the EPM.The 5-HT2A receptor antagonist ketanserin had opposite behavioral effects in CHF and CLF rats.Systemic and IL injections either decreased (CHF) or increased (CLF) anxiety-like behavior.PL injections either decreased (CHF) anxiety-like behavior or had no effect (CLF).

RESUMENLa enfermedad de Parkinson (EP) es la patología neurodegenerativa motora con mayor incidencia a nivel mundial, cuyas causas aún no son claras. Actualmente no existe cura, pero es posible contar con diferentes tratamientos que permiten aliviar algunos de sus síntomas y enlentecer su curso. Debido a la gran cantidad de informaciones, en ocasiones contradictorias sobre los llamados "factores de riesgo" (entendidos éstos como situaciones que pueden exacerbar la posibilidad de aparición de la enfermedad, incluyendo desde la predisposición familiar hasta la exposición prolongada a substancias exógenas), en esta revisión se pretende ofrecer una panorámica actual sobre factores asociados a la aparición de EP. Se revisan también algunos tratamientos que buscan contrarrestar la pérdida de la función dopaminérgica de la substancia nigra (SN) y algunas de las aproximaciones terapéuticas tanto farmacológicas, como por estimulación cerebral profunda (ECP) o por implante celular. Se revisan también investigaciones sobre el potencial terapéutico de compuestos con alta especificidad a receptores colinérgicos (nAChRs) y antagonistas de receptores de adenosina, específicamente del subtipo A2A. Posiblemente durante las próximas décadas, nuestro conocimiento en epigenética pueda arrojar nuevas luces sobre esta interacción, así como sobre las relaciones entre ciertas líneas de microbios intestinales y aparición de EP. En este momento, la alternativa terapéutica que ofrece mayor eficacia es la ECP, sin embargo, a futuro se espera que el desarrollo de nuevas estrategias de implante cerebral pueda ofrecer una cura real de la EP. Palabras claveEnfermedad de Parkinson (EP); estimulación cerebral profunda (ECP); sustancia nigra (SN); núcleo subtálamico (NST); globo pálido interno (GPi). ABSTRACTParkinson's disease (PD) is the most prevalent neurodegenerative motor pathology worldwide, the causes of which are still unclear. Currently there is no cure, but it is possible to have different treatments that allow to alleviate some of its symptoms and slow its course. Due to the large amount of information, sometimes contradictory, about the

Background The bidirectional selection of high and low anxiety-like behavior is a valuable tool for understanding the neurocircuits that are responsible for anxiety disorders. Our group developed two breeding lines of rats, known as Carioca High-and Low-conditioned Freezing (CHF and CLF), based on defensive freezing in the contextual fear conditioning paradigm. A random selected line was employed as a control (CTL) comparison group for both CHF and CLF lines of animals. The present study performed Fos immunochemistry to investigate changes in neural activity in different brain structures among CHF and CLF rats when they were exposed to contextual cues that were previously associated with footshock. Results The study indicated that CHF rats expressed high Fos expression in the locus coeruleus, periventricular nucleus of the hypothalamus (PVN), and lateral portion of the septal area and low Fos expression in the medial portion of the septal area, dentate gyrus, and prelimbic cortex (PL) compared to CTL animals. CLF rats exhibited a decrease in Fos expression in the PVN, PL, and basolateral nucleus of the amygdala and increase in the cingulate and perirhinal cortices compared to CTL animals. Conclusions Both CHF and CLF rats displayed Fos expression changes key regions of the anxiety brain circuitry. The two bidirectional lines exhibit different pattern of neural activation and inhibition with opposing influences on the PVN, the main structure involved in regulating the hypothalamic-pituitary-adrenal neuroendocrine responses observed in anxiety disorders.