Reinforcement omission effects in rats with bilateral lesions in the substantia nigra pars compacta and ventral tegmental area

Reinforcement omission effects (ROEs) are characterized by higher response rates after reinforcement omission than after reinforcement delivery. This pattern of behavior is interpreted in terms of motivational and attentional processes. Recent studies from our laboratory have shown that the amygdala, nucleus accumbens, and medial prefrontal cortex are involved in ROE modulation. Also, the literature has demonstrated a role of other areas such as substantia nigra pars compacta (SNc) and the ventral tegmental area (VTA) in processes related to surprising events, such as prediction error and presentation or omission of an event (exteroceptive stimulus and reinforcement). Since these structures send projections to areas related to ROE modulation such as the amygdala, nucleus accumbens, and prefrontal cortex, the objective of the present study was to determine whether the SNc and VTA also integrate the circuit involved in ROE modulation. Rats were trained on a fixed-interval 12 s with limited-hold 6 s signaled schedule of reinforcement (Pre-lesion training). After acquisition of stable performance, the rats received bilateral neurotoxic lesions of the SNc (Experiment 1) and VTA (Experiment 2). Following postoperative recovery, the rats were submitted to two refresher sessions (Post-lesion training). Subsequently, the training was changed from a 100 to a 50% schedule of reinforcement (Post-lesion testing). In both experiments, the results showed that there was no difference in performance between sham rats and rats with bilateral lesions of the SNc or the VTA.

Neurobiología de las adicciones y procesos de plasticidad involucrados / The Neurobiology of Addiction and the Plasticity Processes Involved

Las evidencias acumuladas en los últimos diez años, indican que las drogas de abuso pueden cooptar los mecanismos de plasticidad en circuitos cerebrales involucrados en las recompensas a reforzadores naturales (comida, bebida, sexo, etc.), resultando en una forma patológica pero poderosa, de memoria y aprendizaje. El circuito involucra esencialmente, el sistema dopaminérgico mesolímbico (area tegmental ventral (VTA), nucleus accumbens (NAcc) y estructuras límbicas asociadas). La plasticidad sináptica en las íreas involucradas incide particularmente en la abstinencia, la recurrencia, la reincidencia y la pérdida del autocontrol. La ínsula y en particular, la ínsula anterior derecha, participa en las percepciones de los estados emocionales corporales que generan las urgencias de consumo y las saliencias de incentivos corporales. Esto se refleja en los estudios imagenológicos funcionales y se confirma por la pérdida del hábito al consumo de tabaco en los casos de lesiones cerebrales en éstas áreas específicas.

Evidence gathered during the past ten years demonstrates that drugs of abuse may co-opt plasticity mechanisms in brain circuits involved in the rewards to natural reinforcements (food, drink, sex, etc.) which results in a pathological but powerful form of memory and learning. The circuit basically involves the mesolimbic dopamine system (ventral tegmental area (VTA), the nucleus accumbens (NAcc) and associated limbic structures). The synaptic plasticity in the areas involved particularly impacts on abstinence, recurrence, recidivism and the loss of self-control. The insula, and the right anterior insula in particular, plays a role in the perceptions of the emotional states of the body that trigger the craving for consumption and the salience of body incentives. This is depicted in functional imaging studies and is demonstrated by the break of the habit of smoking in cases of brain injuries in these specific areas.

Sistemas de motivación y su impacto en la resiliencia: mecanismos neurobiológicos y moleculares implicados / Reward systems and their impact in resilience: neurobiological and molecular mechanisms implicated

La resiliencia en un individuo tiene relación con el potencial de permanecer psicológicamente sano a pesar de estar sometido a situaciones de alto riesgo psicosocial.En esta revisión se aborda el complejo fenotipo de la resiliencia bajo el punto de vista de los sistemas de motivación y del circuito dopaminérgico que involucra al área ventral tegmental (VTA) y al núcleo accumbens (NAc) junto con la participación fundamental del neuropéptido factor neurotrófico derivado del cerebro (BDNF). Lo esencial con respecto a este neuropéptido es que un incremento de su señal en el NAc, producto de un aumento en la descarga neuronal del VTA, promueve un fenotipo susceptible (vulnerable) al stress social, este aumento del BDNF no ocurre en el NAc de los fenotipos resilientes. Otro hecho interesante que se menciona en este artículo, es la existencia de un polimorfismo que ocurre en humanos que tiene relación con el gen del BDNF (G196A, Val66 Met), que impide la liberación de este factor neurotrófico. La presencia de este polimorfismo evidencia, en cierta forma, la existencia de una variabilidad interindividual en la respuesta frente al stress social, concepto que nos acerca a una mirada evolutiva que también se pretende dar en esta revisión. La participación de los sistemas de recompensa en el desarrollo de la resiliencia implica un aspecto que tiene el potencial de continuar estudiándose y contribuir en la aplicación de nuevas estrategias de intervención en salud mental de poblaciones expuestas a condiciones de alto riesgo psicosocial.

Resilience in an individual has relation with the potential to keep psychologically healthy despite of high psychosocial risk situations. In this review, the complex resilience phenotype is analyzed under a viewpoint of the reward systems and the dopaminergic pathways that involves the ventral tegmental area (VTA) and the nucleusaccumbens (NAc), also with the fundamental participation of the brain derived neurotrophic factor (BDNF). An increasing signalling of this neuropeptide in the NAc, as a result of an enhanced neuronal firing from the VTA, produces a susceptible phenotype to social defeat instead of a resilient phenotype that does not show this BDNF increase. Another important issue is the existence of the BDNF gene polymorphism (G196A, Val66 Met) that occurs in humans. This polymorphism inhibits the release of this neuropeptide. This fact explains, in some way, an interindividual variability in the response to social defeat wish brings to us an evolutionary look that this review also pretends to give. The participation of the reward systems in developing resilience is a topic that has the potential to continue studying and by this way contribute to the application of new strategies of intervention in mental health of people exposed to high psychosocial risk conditions.