Susceptibility to express amphetamine locomotor sensitization correlates with dorsolateral striatum bursting activity and GABAergic synapses in the globus pallidus.

Repeated psychostimulant administration results in behavioral sensitization, a process that is relevant in the early phases of drug addiction. Critically, behavioral sensitization is not observed in all subjects. Evidence shows that differential neuronal activity in the dorsolateral striatum (DLS) accompanies the expression of amphetamine (AMPH) locomotor sensitization.

Dendritic Architecture Predicts Firing Pattern in Mouse Ventral Tegmental Area and Substantia Nigra Dopaminergic Neurons.

The firing activity of ventral tegmental area (VTA) and substantia nigra pars compacta (SNc) dopaminergic (DA) neurons is an important factor in shaping DA release and its role in motivated behavior. Dendrites in DA neurons are the main postsynaptic compartment and, along with cell body and axon initial segment, contribute to action potential generation and firing pattern. In this study, the organization of the dendritic domain in individual VTA and SNc DA neurons of adult male mice, and their relationship to spontaneous firing, are described.

Individual Differences in Amphetamine Locomotor Sensitization are Accompanied with Changes in Dopamine Release and Firing Pattern in the Dorsolateral Striatum of Rats.

Not all the people that consume drugs of abuse develop addiction. In this sense, just a percentage of rats express locomotor sensitization after repeated psychostimulant exposure. Neurochemical evidence has shown that locomotor sensitization is associated with changes in dorsolateral striatum (DLS) activity.

Gluconeogenic Enzymes in β-Cells: Pharmacological Targets for Improving Insulin Secretion.

Pancreatic β-cells express the gluconeogenic enzymes glucose 6-phosphatase (G6Pase), fructose 1,6-bisphosphatase (FBP), and phosphoenolpyruvate (PEP) carboxykinase (PCK), which modulate glucose-stimulated insulin secretion (GSIS) through their ability to reverse otherwise irreversible glycolytic steps. Here, we review current knowledge about the expression and regulation of these enzymes in the context of manipulating them to improve insulin secretion in diabetics. Because the regulation of gluconeogenic enzymes in β-cells is so poorly understood, we propose novel research avenues to study these enzymes as modulators of insulin secretion and β-cell dysfunction, with especial attention to FBP, which constitutes an attractive target with an inhibitor under clinical evaluation at present.

Cytosolic phosphoenolpyruvate carboxykinase is expressed in α-cells from human and murine pancreas.

The pancreatic islets of Langerhans, mainly formed by glucagon-producing α-cells and insulin-producing β-cells, are critical for glucose homeostasis. Insulin and glucagon oppositely modulate blood glucose levels in health, but a combined decline in insulin secretion together with increased glucagon secretion contribute to hyperglycemia in diabetes. Despite this bi-hormonal dysregulation, most studies have focused on insulin secretion and much less is known about glucagon secretion.