Perineuronal nets (PNNs) are unique extracellular matrix structures that wrap around certain neurons in the CNS during development and control plasticity in the adult CNS. They appear to contribute to a wide range of diseases/disorders of the brain, are involved in recovery from spinal cord injury, and are altered during aging, learning and memory, and after exposure to drugs of abuse. Here the focus is on how a major component of PNNs, chondroitin sulfate proteoglycans, control plasticity, and on the role of PNNs in memory in normal aging, in a tauopathy model of Alzheimer's disease, and in drug addiction. Also discussed is how altered extracellular matrix/PNN formation during development may produce synaptic pathology associated with schizophrenia, bipolar disorder, major depression, and autism spectrum disorders. Understanding the molecular underpinnings of how PNNs are altered in normal physiology and disease will offer insights into new treatment approaches for these diseases.

The results of the present study suggest that the selective inactivation of acetaldehyde blocked the rewarding, but not aversive, effects of ethanol and support the role of this ethanol metabolite in the affective properties of ethanol.

No abstract

No abstract

a b s t r a c tMany 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.

Marta Miquel; Rebeca Toledo; Luis I Garcia ; Genaro A Coria-Avila¸ Jorge Manzo. 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 control.Key words: cerebellum, drug addiction, alcohol, morphine, cocaine, amphetamine, endocannabinoids, sensitization, conditioned emotional memories, cerebellar plasticity 3 THE CEREBELLUM: MORE THAN WHAT WE THOUGHTVery recently, Masao Ito [1] and Narender Ramnani [2] published two excellent and exhaustive reviews on the cerebellum and its functions. Both are highly recommended papers to get a broad perspective on past and current research in this topic. Surely the lesson to be learned from both articles is that later developments in cerebellar research situate functions of the cerebellum beyond motor control. The assumption that the cerebellum controls movement came from medical observations in the mid 19 th and the beginning of the 20 th century [1, 3]. Neurologists observed that lesions in this structure resulted in difficulties in coordinating movement, and experimental physiologists showed that after removing the cerebellum a lack of motor coordination was produced. In the sixties, a specialized role for the cerebellum in the learning of motor patterns was proposed, initially in conventional mo...

Behavioral effects produced by acetaldehyde and ethanol are blocked when animals are treated with D-penicillamine, an effective sequestration agent for acetaldehyde. These results suggest that some of the psychopharmacological effects, classically attributed to ethanol, could be mediated by its first metabolite, acetaldehyde.

Versión / Versió:Preprint Conflict of Interest (COI) StatementThe authors of the present manuscript declare no conflict of interest. AbstractDue to its capital 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 focused on neuronal systems that store and control drug-conditioned memories have found cerebellar activations during the retrieval of drug-associated cues memory. However, at the preclinical 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 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.