The purpose of this article is to assist institutions in advancing their efforts to support research mentorship. The authors begin by describing how institutions can shape the key domains of research mentorship: (1) the criteria for selecting mentors, (2) incentives for motivating faculty to serve effectively as mentors, (3) factors that facilitate the mentor-mentee relationship, (4) factors that strengthen a mentee's ability to conduct research responsibly, and (5) factors that contribute to the professional development of both mentees and mentors. On the basis of a conceptual analysis of these domains as currently documented in the literature, as well as their collective experience examining mentoring programs at a range of academic medicine institutions and departments, the authors provide a framework that leaders of institutions and/or departments can adapt for use as a tool to document and monitor policies for guiding the mentorship process, the programs/activities through which these policies are implemented, and the structures that are responsible for maintaining policies and implementing programs. The authors provide an example of how one hypothetical institution might use the self-assessment tool to track its policies, programs, and structures across the key domains of research mentorship and, on the basis of this information, identify a range of potential actions to strengthen its research mentoring efforts. The authors conclude with a brief discussion of the limitations of the self-assessment tool, the potential drawbacks and benefits of the overall approach, and proposed next steps for research in this area.

Benzodiazepines exert most of their pharmacological effects by a selective facilitation of the postsynaptic actions of GABA. Clinical, behavioural and electrophysiological studies have shown reduced drug response following chronic benzodiazepine administration. We present here electrophysiological evidence for decreased postsynaptic sensitivity to GABA following chronic benzodiazepine administration as measured by the direct iontophoretic application of GABA and serotonin onto serotonergic cells in the midbrain dorsal raphe nucleus (DRN), known to receive GABAergic input. The subsensitivity to GABA was found to be dose dependent and was seen when diazepam administration was three weeks or longer. Further, acute injection of the specific benzodiazepine antagonist, Ro15-1788, was found to reverse rapidly the decrease in GABA sensitivity observed in chronically diazepam-treated animals without altering GABA sensitivity in vehicle-treated rats. Decreased response to chronic benzodiazepines does not appear to be consistently related to alterations in the number or affinity of receptors for benzodiazepines. Our studies of radioligand-binding showed a decrease in the ability of GABA to enhance benzodiazepine binding in cerebral cortical membranes from chronic diazepam-treated animals without significant changes in benzodiazepine binding site density or affinity.

Recent studies suggest that the mesoaccumbens dopamine system undergoes neurochemical alterations as a result of restricted feeding conditions with access to sugars. This effect appears to be similar to the neuroadaptation resulting from drugs of abuse and may underlay some pathological feeding behaviors. To further investigate the cellular mechanisms of these alterations, the present study used quantitative autoradiography and in situ hybridization to assess dopamine membrane transporter (DAT) protein density and mRNA expression in restricted-fed and free-fed adult male rats. The restricted feeding regimen consisted of daily limited access to either a normally preferred sucrose solution (0.3 M) or a less preferred chow in a scheduled (i.e., contingent) fashion for 7 days. Restricted-fed rats with the contingent sucrose access lost less body weight, ate more total food, and drank more fluid than free-fed, contingent food, or noncontingent controls. In addition, these animals had selectively higher DAT binding in the nucleus accumbens and ventral tegmental area. This increase in protein binding also was accompanied by an increase in DAT mRNA levels in the ventral tegmental area. In contrast to the restricted-fed groups, no differential effect in DAT regulation was observed across free-fed groups. The observed alteration in behavior and DAT regulation suggest that neuroadaptation in the mesoaccumbens dopamine system develops in response to repeated feeding on palatable foods under dietary constraints. This supports the notion that similar cellular changes may be involved in restrictive eating disorders and bingeing.

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Loss of motor function in Parkinson's disease is due in part to degeneration of dopamine (DA) neurons. Pharmacological evidence suggests that the mitogen-activated protein kinase signaling pathways involving extracellular signal-regulated kinases (ERKs) play important roles in neuroprotection of DA neurons. However, the relative roles of the several ERK isoforms in the viability of DA neurons have not yet been determined. In the present study, we investigated the contributions of ERK5, as well as ERK1/2, to MN9D cell survival under basal conditions and in response to 6-hydroxydopamine (6-OHDA). We observed that U0126, an inhibitor of ERK activation, decreased basal survival of these cells. To differentiate between ERK1/2 and ERK5, cells were transfected with a dominant negative form of either ERK5 or MEK1, the upstream activator of ERK1/2. Transfection of MN9D cells with either dominant negative construct mimicked U0126, reducing cell survival. Moreover, transfection of the cells in such a way as to increase ERK5 or ERK1/2 activity inhibited 6-OHDA-induced cell death, although this effect was significant only in the case of ERK1/2 activation. These studies suggest that activations of ERK5 and ERK1/2 both promote basal DA cell survival and that ERK1/2 also protects DA cells from oxidative stress. These are the first studies to demonstrate a role for ERK5 in DA neuronal survival and to investigate the relative roles of ERK1/2 and ERK5 in basal DA survival and neuroprotection from oxidative stress.