Introduction to Social Neuroscience: Gene, Environment, Brain, Body

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/87184/1/j.1749-6632.2011.06154.x.pd

Hormonal effects on extra- and intraneural mechanism: an integrative approach

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/30396/1/0000015.pd

Hydrophobic Residues of the D 2 Dopamine Receptor Are Important for Binding and Signal Transduction

Dopamine receptors belong to the seven transmembrane helix-containing, G protein-coupled receptor superfamily. Mutagenesis studies suggest that dopamine and its analogues interact with aspartate-114 in helix 3 and two helix 5 serines (194 and 197) of the D 2 receptor. In addition to these amino acids, hydrophobic residues within the receptor core may be important not only for binding but also for receptor activation. Described is a site-directed mutagenesis investigation into the roles of these hydrophobic residues in the long isoform of the human D 2 receptor. Replacement of helix 6 phenylalanines (389 or 390) with alanines resulted in disrupted binding to several agonists and antagonists and impaired inhibition of adenylyl cyclase activity. Replacement of the helix 5 phenylalanine-198 with an alanine selectively disrupted [ 3 H]N-0437 binding, whereas the affinities for other agonists and antagonists remained unchanged. This mutant remained functionally intact when stimulated with dopamine or bromocriptine. Replacement of the helix 7 phenylalanine-411 or the helix 6 leucine-387 with alanines produced receptors that bound agonists well but were unable to inhibit adenylyl cyclase. Based on these data, two conserved helix 6 phenylalanines (389 and 390) appear to be crucial for ligand binding, and phenylalanine-411 in helix 7 and leucine-387 in helix 6 may be important for propagating conformational changes from the agonist binding site(s) to G protein coupling domain(s) of the D 2 receptor.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/65921/1/j.1471-4159.1995.65052105.x.pd

Selective Alterations of Opiate Receptor Subtypes in Mono sodium Glutamate-Treated Rats

Neonatal treatment of rats with monosodium glutamate (MSG) has been demonstrated to destroy cell bodies of neurons in the arcuate nucleus including the brain beta-endorphin (B-END) system. The effects on opiate receptors of the loss of B-END is unknown. Neonatal rats were treated with MSG as previously described. After reaching maturity (7-9 months), MSG-treated rats and litter-matched untreated control rats were decapitated and brains dissected into brain regions. Opiate receptor assays were run with [ 3 H]morphine (mu receptor ligand) and [ 3 H]D-alanine 2 -D-leucine 5 (DADL) enkephalin (delta receptor ligand) for each brain region for both MSG and control rats simultaneously. Scatchard plot analyses showed a selective increase in delta receptors in the thala-mus only. No corresponding change in mu receptors in the thalamus was found. The cross-competition IC 50 data supported this conclusion, showing a loss in the potency of morphine in displacing [ 3 H]DADL enkephalin in the thalamus of MSG-treated rats. This shift in delta receptors produced an IC 50 displacement pattern in thalamus, ordinarily a mu-rich area, similar to that of striatum or cortex, delta-rich areas, again indicating an increase in delta receptors. Similar changes in delta receptors in other brain regions were not found. These results represent one of the few examples of a selective and localized shift in delta with no change in mu sites. Furthermore, the delta increase may reflect an up-regulation of the receptors in thalamus after chronic loss of the endogenous opioid B-END.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/65552/1/j.1471-4159.1983.tb08126.x.pd

Plasma beta-endorphin-like immunoreactivity, self reported pain perception and anxiety levels in women during pregnancy and labor

Plasma Beta-endorphin (B-END) immunoreactivity was measured in 19 men, 16 women at midcycle, and ten pregnant women at various points in their pregnancies. There is a significant difference between the levels measured in males and females (t = 3.74, df = 31, p = .0007). Pregnant women demonstrated a steady increase in plasma Beta-End-like immunoreactivity between second and third trimester and through labor. The levels dropped rapidly postpartum. The material being measured is predominantly B-end-sized. Psychological studies indicate that these changes are not strongly correlated with pain perception or self-reported anxiety levels.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/23837/1/0000076.pd

Pulse-chase studies of the POMC/Beta-endorphin system in the pituitary of acutely and chronically stressed rats

Experiments were carried out to determine whether stress induces biochemical changes in the pro-opiomelanocortin (POMC) system in anterior (AL) and intermediate-posterior lobe (IPL) of rat. In a series of pulse-chase experiments, acute stress led to an increase in POMC biosynthesis and shorter half-life in AL. However, when the animals were chronically stressed, the AL no longer exhibited increased POMC synthesis. On the other hand, in the IPL, acute stress did not produce any biochemical changes, but chronic stress led to an increase in POMC synthesis and shorter half-life. These data suggest that AL and IPL are affected by acute and/or chronic exposure to stress in opposite directions and that the POMC system in AL may play an important role in stress-induced analgesia.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/23803/1/0000041.pd

The NMDA receptor antagonist MK-801 increases morphine catalepsy and lethality

Interactions between excitatory amino acids and opioids were examined by studying the ability of the noncompetitive N-methyl-D-aspartate (NMDA) receptor antagonist MK-801 to affect morphine catalepsy and lethality. MK-801 (0.3 mg/kg) reduced the ED50 for morphine-induced catalepsy from approximately 30 mg/kg to less than 10 mg/kg, and reduced the LD50 for morphine from approximately 100 mg/kg to approximately 10 mg/kg. Lower doses of MK-801 did not affect morphine catalepsy or lethality. MK-801, in the absence of morphine, produced no catalepsy or lethality at doses up to 3.0 mg/kg; at 0.3 mg/kg MK-801 caused weaving, body rolling and ataxia, as previously described, while at 3.0 mg/kg animals appeared to lose muscle tone, becoming limp. These results demonstrate that blockade of NMDA receptors can dramatically potentiate morphine catalepsy and lethality, and suggest a potential dangerous interaction with opioids in the clinical use of NMDA receptor antagonists.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/29443/1/0000525.pd

Letters to the Editor

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/25515/1/0000056.pd

Steady state levels of pro-dynorphin-related end products in the striatum and substantia nigra of the adult rhesus monkey

Analysis of an acid extract of the striatum of the rhesus monkey revealed that the molar ratio of dynorphin A(1-8)-sized material and dynorphin (A(1-17)-sized material is approximately 1:1. In addition, the molar ratios of the dynorphin A-related end products to both dynorphin B(1-13)-sized material and alpha-neo-endorphin-sized material were approximately 1:1. Fractionation of an acid extract of the substantia nigra by gel filtration and reverse phase HPLC revealed the following molar ratios for pro-dynorphin-related end products. The molar ratio of dynorphin A(1-8) to dynorphin A(1-17) is approximately 6:1. The molar ratios of dynorphin A-related end products to dynorphin B(1-13) and alpha-neo-endorphin were approximately 0.5 and 0.8, respectively. Comparisons between proteolytic processing patterns of pro-dynorphin in the striatum and the substantia nigra of the rhesus monkey are considered. In addition, comparisons between pro-dynorphin processing in the substantia nigra of the rhesus monkey and the substantia nigra of the rat [4] are discussed.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/25852/1/0000415.pd

Changes in releasability of ACTH and Beta-endorphin with chronic stress

The activation of the hypothalamic pituitary adrenal axis by stress is well-known. Using inescapable intermittent footshock as a stressor in rats, we have previously demonstrated a rise in circulating plasma Beta-endorphin/Beta-LPH which parallels the rise in plasma ACTH, the primary POMC derived peptides released by anterior lobe. In addition, the rise in ACTH is accompained by approximately a tenfold rise in plasma corticosteroids. Short term anterior lobe pituitary cultures from rats who have received inescapable intermittent footshock for 30 minutes show a blunted dose response curve to the ACTH releasing secretagogues arginine vasopressin (AVP) and ovine corticotropin releasing factor (oCRF). Similarly a blunted dose response curves to secretagogues can be seen by either the addition of dexamethasone (0.5 nM) to the culture medium or pretreatment of the rats with 1 mg dexamethasone intraperitoneally 90 minutes prior to decapitation. Thus, glucocorticoids may play a role in the blunted response to secretagogues seen in anterior lobe cultures from acutely stressed rats. We now report that chronically stressed rats exhibit increased releasability of ACTH and Beta-endorphin/Beta-LPH products by oCRF, suggesting an increase of the peptides in the releasable pool.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/25776/1/0000337.pd