Role of the mesoamygdaloid dopamine projection in emotional learning

Amygdala dopamine is crucially involved in the acquisition of Pavlovian associations, as measured via conditioned approach to the location of the unconditioned stimulus (US). However, learning begins before skeletomotor output, so this study assessed whether amygdala dopamine is also involved in earlier 'emotional' learning. A variant of the conditioned reinforcement (CR) procedure was validated where training was restricted to curtail the development of selective conditioned approach to the US location, and effects of amygdala dopamine manipulations before training or later CR testing assessed. Experiment 1a presented a light paired (CS+ group) or unpaired (CS- group) with a US. There were 1, 2 or 10 sessions, 4 trials per session. Then, the US was removed, and two novel levers presented. One lever (CR+) presented the light, and lever pressing was recorded. Experiment 1b also included a tone stimulus. Experiment 2 applied intra-amygdala R(+) 7-OH-DPAT (10 nmol/1.0 A mu l/side) before two training sessions (Experiment 2a) or a CR session (Experiment 2b). For Experiments 1a and 1b, the CS+ group preferred the CR+ lever across all sessions. Conditioned alcove approach during 1 or 2 training sessions or associated CR tests was low and nonspecific. In Experiment 2a, R(+) 7-OH-DPAT before training greatly diminished lever pressing during a subsequent CR test, preferentially on the CR+ lever. For Experiment 2b, R(+) 7-OH-DPAT infusions before the CR test also reduced lever pressing. Manipulations of amygdala dopamine impact the earliest stage of learning in which emotional reactions may be most prevalent

NMDA Receptor Stimulation Induces Reversible Fission of the Neuronal Endoplasmic Reticulum

With few exceptions the endoplasmic reticulum (ER) is considered a continuous system of endomembranes within which proteins and ions can move. We have studied dynamic structural changes of the ER in hippocampal neurons in primary culture and organotypic slices. Fluorescence recovery after photobleaching (FRAP) was used to quantify and model ER structural dynamics. Ultrastructure was assessed by electron microscopy. In live cell imaging experiments we found that, under basal conditions, the ER of neuronal soma and dendrites was continuous. The smooth and uninterrupted appearance of the ER changed dramatically after glutamate stimulation. The ER fragmented into isolated vesicles in a rapid fission reaction that occurred prior to overt signs of neuronal damage. ER fission was found to be independent of ER calcium levels. Apart from glutamate, the calcium ionophore ionomycin was able to induce ER fission. The N-methyl, D-aspartate (NMDA) receptor antagonist MK-801 inhibited ER fission induced by glutamate as well as by ionomycin. Fission was not blocked by either ifenprodil or kinase inhibitors. Interestingly, sub-lethal NMDA receptor stimulation caused rapid ER fission followed by fusion. Hence, ER fission is not strictly associated with cellular damage or death. Our results thus demonstrate that neuronal ER structure is dynamically regulated with important consequences for protein mobility and ER luminal calcium tunneling

Molecular Mechanisms Associated with Nicotine Pharmacology and Dependence.

Tobacco dependence is a leading cause of preventable disease and death worldwide. Nicotine, the main psychoactive component in tobacco cigarettes, has also been garnering increased popularity in its vaporized form, as derived from e-cigarette devices. Thus, an understanding of the molecular mechanisms underlying nicotine pharmacology and dependence is required to ascertain novel approaches to treat drug dependence. In this chapter, we review the field's current understanding of nicotine's actions in the brain, the neurocircuitry underlying drug dependence, factors that modulate the function of nicotinic acetylcholine receptors, and the role of specific genes in mitigating the vulnerability to develop nicotine dependence. In addition to nicotine's direct actions in the brain, other constituents in nicotine and tobacco products have also been found to alter drug use, and thus, evidence is provided to highlight this issue. Finally, currently available pharmacotherapeutic strategies are discussed, along with an outlook for future therapeutic directions to achieve to the goal of long-term nicotine cessation

The development of sensitization to the psychomotor stimulant effects of amphetamine is enhanced in a novel environment

Two experiments were designed to assess the effect of a “novel” environment on the development of sensitization to the psychomotor activating effects of d -amphetamine. In the first experiment, rats with a unilateral 6-hydroxydopamine lesion of the mesostriatal dopamine system received ten daily injections of amphetamine (2 mg/kg), either in their home cages or in novel test cages. The home and novel cages were physically identical (cylindrical transparent buckets), but one group lived and were tested in these cages, whereas the other group was transported from the stainless steel hanging cages where they lived to these novel test cages, for each test session. The first injection of amphetamine produced significantly more rotational behavior in animals tested in a novel environment than in animals tested at home. In addition, animals tested in a novel environment showed greater sensitization than animals tested at home, so the difference between the two groups was even more pronounced following the last injection. In a second experiment, locomotor activity was quantified in rats that received ten injections of either saline or 1.5 mg/kg amphetamine, in their home cages or in a physically identical novel environment. Again, there was a significantly greater locomotor response to the first injection of amphetamine, and greater sensitization, in animals tested in a novel environment than in animals tested at home. These data indicate that environmental factors can exert a large effect on the susceptibility to sensitization, and mechanisms by which this may occur are discussed.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/46345/1/213_2005_Article_BF02246217.pd

Life course transitions and the future of fandom

We explore the future of media fandom through integrating insights from gerontology, human development, fan studies, and marketing. Given population aging and the dismantling of the normative 20th-century life course, along with rapid changes in the extent to which our lives are mediated, fandom is undergoing significant modification. We focus on how new findings on emotional maturation over the life course and scholarly identification of self-narrativization as a resource for 21st-century aging suggest ways that fandom may change over time. © The Author(s) 2011