Why should we keep the cerebellum in mind when thinking about addiction?

Increasing evidence has involved the cerebellum in functions beyond the sphere of motor control. In the present article, we review evidence that involves the cerebellum in addictive behaviour. We aimed on molecular and cellular targets in the cerebellum where addictive drugs can act and induce mechanisms of neuroplasticity that may contribute to the development of an addictive pattern of behaviour. Also, we analyzed the behavioural consequences of repetitive drug administration that result from activitydependent changes in the efficacy of cerebellar synapses. Revised research involves the cerebellum in drug-induced long-term memory, druginduced sensitization and the perseverative behavioural phenotype. Results agree to relevant participation of the cerebellum in the functional systems underlying drug addiction. The molecular and cellular actions of addictive drugs in the cerebellum involve long-term adaptative changes in receptors, neurotransmitters and intracellular signalling transduction pathways that may lead to the re-organization of cerebellar microzones and in turn to functional networks where the cerebellum is an important nodal structure. We propose that drug induced activity-dependent synaptic changes in the cerebellum are crucial to the transition from a pattern of recreational drug taking to the compulsive behavioural phenotype. Functional and structural modifications produced by drugs in the cerebellum may enhance the susceptibility of fronto-cerebellar circuitry to be changed by repeated drug exposure. As a part of this functional reorganization, drug-induced cerebellar hyper-responsiveness appears to be central to reducing the influence of executive control of the prefrontal cortex on behaviour and aiding the transition to an automatic mode of contro

Neurobiology of social attachments

Many types of social attachments can be observed in nature. We discuss the neurobiology of two types (1) intraspecific (with a partner) and (2) parental (with the offspring). Stimuli related to copulation facilitate the first, whereas pregnancy, parturition and lactation facilitate the second. Both types develop as consequence of cohabitation. These events seem to stimulate similar neural pathways that increase (1) social recognition, (2) motivation, reward; and (3) decrease fear/anxiety. Subregions of the amygdala and cortex facilitate social recognition and also disinhibition to decrease rejection responses. The interrelationship between MeA, BNST, LS may mediate the activation of NAcc via the mPOA to increase motivation and reward. Cortical areas such as the ACC discriminate between stimuli. The interaction between OT and D2-type receptors in NAcc shell facilitates intraspecific attachment, but D1-type appears to facilitate parental attachment. This difference may be important for maternal females to direct their attention, motivation and expression of attachment toward the appropriate target.Cuerpo Académico UV-CA-28 Neurociencias. Grant SEP-CONACYT (167773) to GACA

Involving the cerebellum in cocaine-induced memory: pattern of CFOS expression in mice trained to acquire conditioned preference for cocaine

Because of its primary role in drug-seeking, consumption and addictive behaviour, there is a growing interest in identifying the neural circuits and molecular mechanisms underlying the formation, maintenance and retrieval of drug-related memories. Human studies, which focused on neuronal systems that store and control drug-conditioned memories, have found cerebellar activations during the retrieval of drug-associated cue memory. However, at the pre-clinical level, almost no attention has been paid to a possible role of the cerebellum in drug-related memories. In the present study, we ought to fill this gap by aiming to investigate the pattern of neuronal activation (as revealed by cFos expression) in different regions of the prefrontal cortex and cerebellum of mice trained to develop conditioned preference for an olfactory stimulus (CS+) paired with cocaine. Our results indicate that CS+ preference was directly associated with cFos expression in cells at the apical region of the granule cell layer of the cerebellar vermis; this relationship being more prominent in some specific lobules. Conversely, cFos+ immunostaining in other cerebellar regions seems to be unrelated to CS+ preference but to other aspects of the conditioning procedure. At the prefrontal cortex, cFos expression seemed to be related to cocaine administration rather than to its ability to establish conditioned preference. The present results suggest that as it has been observed in some clinical studies, the cerebellum might be an important and largely overlooked part of the neural circuits involved in generating, maintaining and/or retrieving drug memories

Have we been ignoring the elephant in the room? Seven arguments for considering the cerebellum as part of addiction circuitry

Addiction involves alterations in multiple brain regions that are associated with functions such as memory, motivation and executive control. Indeed, it is now well accepted that addictive drugs produce long-lasting molecular and structural plasticity changes in corticostriatal-limbic loops. However, there are brain regions that might be relevant to addiction other than the prefrontal cortex, amygdala, hippocampus and basal ganglia. In addition to these circuits, a growing amount of data suggests the involvement of the cerebellum in many of the brain functions affected in addicts, though this region has been overlooked, traditionally, in the addiction field. Therefore, in the present review we provide seven arguments as to why we should consider the cerebellum in drug addiction. We present and discuss compelling evidence about the effects of drugs of abuse on cerebellar plasticity, the involvement of the cerebellum in drug-induced cue-related memories, and several findings showing that the instrumental memory and executive functions also recruit the cerebellar circuitry. In addition, a hypothetical model of the cerebellum's role relative to other areas within corticostriatal-limbic networks is also provided. Our goal is not to review animal and human studies exhaustively but to support the inclusion of cerebellar alterations as a part of the physiopathology of addiction disorder.This work was supported by grants and fellowships: FPU12/04059, PPF 2015 (15I082.01/1) and UJI (14I307.01/1). We also thank Timothy Attwood Gibbons for the English revision of the manuscript

Cerebellar hallmarks of conditioned preference for cocaine

Pavlovian conditioning tunes the motivational drive of drug-associated stimuli, fostering the probability of those environmental stimuli to promote and trigger drug seeking and taking. Interestingly, different areas in the cerebellum are involved in the formation and long-lasting storage of Pavlovian emotional memory. Very recently, we have shown that conditioned preference for an odour associated with cocaine was directly correlated with cFOS expression in cells at the dorsal region of the granule cell layer of the cerebellar vermis. The main goal of the current investigation was to further extend the description of cFOS-IR patterns in cerebellar circuitry after training mice in a cocaine-odour Pavlovian conditioning procedure, including now the major inputs (the inferior olive and pontine nuclei) and one of the output nuclei (the medial deep nucleus) of the cerebellum. The results showed that the cerebellar hallmark of preference towards an odour cue associated to cocaine is an increase in cFOS expression in the dorsal part of the granule cell layer. cFOS-IR levels expressed in the granule cell layer of mice that did not show cocaine conditioned preference did not differ from the basal levels. Remarkably, mice subjected to a random cocaine-odour pairing procedure (the unpaired group) exhibited higher cFOS-IR in the inferior olive, the pontine nuclei and in the deep medial nucleus. Therefore, our findings suggest that inputs and the output of cerebellar circuitry are enhanced when contingency between the CS+ and cocaine is lacking

The Brain-Like Enteric Nervous System

Understanding the autonomic supply at the gastrointestinal tract is one of the significant challenges for science. Its complex network of neurons exists on a broad evolutionary scale, from Hydra to mammals, and in a higher number than those found in the vertebrate spinal cord. Inside the gastrointestinal tract, enteric neurons regulate several functions with intrinsic processes and communicate with the other complex known as the microbiome. Outside the gastrointestinal tract, the enteric neurons project to the brain stem and spinal cord via the gut–brain axis. Furthermore, this enteric system has close functional relationships with the immune system for a rapid response to unhealthy food. The present chapter focuses on the structure, function, and pathologies of the enteric nervous system

Cognición en perros: revisión y reporte de caso

Cognition in dogs involves mental processes of attention, memory, and comprehension of signs to create new knowledge in order to facilitate problem solving. Related literature debates about the existence of these processes in dogs because of the resemblance between cognition and behavioral modifications. In this review we describe some studies on dog abilities comparable with those of a toddler. We also discuss other cases of dogs with the ability to memorize hundreds of objects by name, and capable of identifying a new one by excluding the already known. Throughout the document we point out at the many dog abilities that may indicate cognition processes.El estudio de la cognición en perros implica explorar sus procesos mentales de atención, memoria, y comprensión de señales para crear nuevo conocimiento y utilizar dichos procesos para la solución de problemas. En algunas ocasiones los resultados de estudios en perros son debatibles por la delgada línea que divide a la cognición verdadera de las meras modificaciones comportamentales. En esta breve revisión se exponen algunos estudios sobre las habilidades de los perros para seguir e interpretar señales humanas con el fin de resolver problemas comparables a un niño de dos años. Además, discutimos los casos de perros que aprendieron a memorizar los nombres de varias centenas de objetos y a inferir el nombre de uno nuevo, basándose en la exclusión de los ya conocidos y responder correctamente cuando se solicita un objeto por su nombre propio o por su nombre común. También hacemos énfasis en las habilidades potenciales que un perro puede desarrollar mediante el uso de sus procesos cognitivos

El comportamiento homosexual y sus bases neurales

Objective: Redefine the concept of homosexual behavior and its neural bases, and to discuss the role of conditioning on learnt homosexual behaviors. Development: We propose a behavioral continuum in which animals and humans may display appetitive, precopulatory, consummatory or postconsummatory homosexual behaviors with variable intensity and duration. We discuss the role of brain dimorphism on sexual behavior and partner preference. In addition, we show evidence indicating that animals may display learnt social preferences that switch into homosexual preferences if they spent sufficient time of cohabitation with an individual of the same sex under the effect of dopamine type D2 agonists. Conclusion: The evidence in this article suggests that homosexual behavior may be subtle or explicit, transitory or long-lasting, as a result of the computation that results from the activity of neurocircuitries organized by hormones during perinatal periods and by learning during later periods of life.Objetivo: Redefinir el concepto de comportamiento homosexual analizando sus bases apetitivas, precopulatorias, consumatorias y posconsumatorias; así como analizar las bases neurales y el papel del aprendizaje en el comportamiento homosexual. Desarrollo: Proponemos un continuum comportamental con el cual los humanos y animales muestran comportamientos homosexuales de expresión y duración variable. Se discute el papel del dimorfismo sexual del cerebro y la evidencia que lo correlaciona con el comportamiento y las preferencias sexuales. También se muestra evidencia reciente que sugiere que a través del condicionamiento, los animales pueden desplegar preferencias que pasan de lo social a lo homosexual de manera temporal si pasaron suficiente tiempo junto a la pareja del mismo sexo, bajo la influencia de agonistas para el receptor de dopamina tipo D2. Conclusión: la discusión en este artículo sugiere que el comportamiento homosexual puede ocurrir de manera sutil o explícita, temporal o permanentemente, dependiendo del cálculo que resulta de la actividad de neurocircuitos organizados por hormonas en periodos perinatales junto con aquellos circuitos organizados por el aprendizaje en periodos posteriores

Juvenile play conditions sexual partner preference in adult female rats

Rats can display a conditioned partner preference for individuals that bear an odor previously associated with sexual reward. Herein we tested the possibility that odors associated with the reward induced by social play in prepubescent rats would induce a conditioned partner preference in adulthood. Two groups of 31-day-old, single-housed female rats were formed, and were given daily 30-min periods of social play with scented females. In one group, almond scent was paired with juvenile play during conditioning trials, whereas lemon scent functioned as a novel odor in the final test. The counterbalanced group received the opposite association. At age 42, females were tested for play partner preference with two males, one almond-scented and one lemon-scented. In both groups females displayed a play partner preference only for males scented with the paired odor. They were ovariectomized, hormone-primed, and at age 55 were tested for sexual partner preference with two scented stud males. Females displayed a sexual preference towards males scented with the paired odor as observed with more visits, solicitations, hops and darts, intromissions and ejaculations. These results indicate that olfactory stimuli paired with juvenile play affects later partner choice for play as well as for sex in female rats

Sexual reward induces Fos In the cerebellum of female rats

The cerebellum is generally considered a neural structure specialized in motor control and recent imaging data suggest its role in sexual behavior. Herein, we analyzed the pattern of Fos immunoreactivity (Fos-IR) in the cerebellum of female rats allowed to pace copulation as a model of sexual reward in rodents. Ovariectomized, hormone-primed, sexually naïve females formed three groups: Pacing, Nonpacing and Control. Pacing occurred in arenas bisected by a middle divider that allowed only females to control sexual interaction with stud males. For nonpaced copulation the divider was removed, and control females were allowed to pace in chambers without a male. Fos-IR was analyzed in granule and Purkinje layers of the 10 cerebellar lobules, and in the fastigial deep nucleus (FDN). Results indicated that Pacing females expressed more Fos-IR in the granule layer compared to Nonpacing and Controls, and more Fos-IR in Purkinje compared to Nonpacing. No differences were observed in FDN. Such response cannot be explained with motor activity because Pacing females moved less in general. We discuss the role of the cerebellum and its connections in the sexual reward induced by pacing