Sunday, November 28, 2021

Comments by martha

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  • The memory-enhancing dose (1 mg/kg MPH) showed little evidence of reinforcement. In contrast, 10 mg/kg MPH not only produced sensitization, place preference, and a marked stimulating effect, but it also impaired memory. This dissociation is supported by our observation that memory-enhancing doses of AMPH (0.005 mg/kg) and COC (1.5 mg/kg) also showed little evidence of reinforcement, while high, addictive, doses impaired memory (Fig. 4). Together, these results substantiate the view that psychostimulant dosage explains the “paradox” of cognitive enhancements in patient populations and cognitive deficits in addicts (Rapoport et al. 1980; Ellinwood et al. 1998; Rapoport and Inoff-Germain 2002; Berridge and Devilbiss 2011; Wood et al. 2013). As dosage dramatically dissociates psychostimulants’ procognitive and reinforcing effects, it is likely that one can develop an MPH-like drug, which retains all of MPH’s procognitive effects, but lacks any reinforcing effects. Though, to date, such efforts have been limited.

    Overall, we found a clear long-term enhancement of memory by MPH at doses similar to those prescribed for ADHD; these memory-enhancing effects were not confounded by effects on locomotion or anxiety and were readily dissociable from the reinforcing effects seen at high doses. Together, our data suggest that fear conditioning will be an especially fruitful platform for modeling the effects of psychostimulants on LTM in drug development
    Animal model of methylphenidate’s long-term memory-enhancing effects

    Stephanie A. Carmack1,
    Kristin K. Howell1,
    Kleou Rasaei1,
    Emilie T. Reas2 and
    Stephan G. Anagnostaras1,2,3

  • “SSRIs are known to increase adult neurogenesis…”

    “The two phases of neurogenesis depend on the age of the adult-generated neurons. Shortly after they are born, newly generated granule cells migrate into the granule cell layer of the DG, and by ∼2 wk they begin to make functional afferent and efferent connections (Zhao et al. 2006; Toni et al. 2007, 2008). It is the process of establishing new synaptic connections that alters the architecture of existing DG-CA3 networks, perhaps leading to degradation (or loss) of information already stored in those connections. However, as these new neurons continue to mature, they enter the second phase in which they acquire the potential to store memory (or become part of the memory trace). For example, immediate early gene mapping studies suggest that adult-generated neurons maximally contribute to hippocampal memory once they are four or more weeks in age (Kee et al. 2007; Stone et al. 2011b). Indeed, sufficiently mature adult-generated neurons have two key properties that may facilitate their ability to store memories. First, new neurons have “new” (silent?) synapses that may be specifically dedicated to storing new memories, and, second, new neurons are transiently more excitable and more plastic than their mature counterparts and, therefore, perhaps more readily incorporated into a memory trace.”

    Infantile amnesia: A neurogenic hypothesis

    Sheena A. Josselyn1,2,3,4 and
    Paul W. Frankland1,2,3