Philip S. Portoghese

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We showed previously that cAMP response element-binding protein (CREB) within the nucleus accumbens (NAc) of rats regulates immobility in the forced swim test (FST), an assay used to study depression. Because CREB regulates expression of dynorphin (which acts at kappa-opioid receptors) in NAc neurons, these findings raised the possibility that(More)
The opioid antagonist activities of two bivalent ligands, BNI and nor-BNI, have been evaluated in smooth muscle preparations and in mice. Both ligands are highly potent and selective as kappa opioid receptor antagonists, with relatively feeble blocking activity at mu and delta opioid receptors. BNI and nor-BNI represent the first highly selective kappa(More)
RATIONALE Elevations in cAMP response element binding protein (CREB) function within the mesolimbic system of rats reduce cocaine reward in place conditioning studies and increase immobility in the forced swim test. Each of these behavioral adaptations can be interpreted as a depressive-like effect (i.e., anhedonia, despair) that may reflect reduced(More)
Kappa opioid agonists attenuate some neurochemical and behavioral effects of cocaine and are being considered as potential treatments for cocaine dependence. The present study examined the effects of two kappa opioid agonists, the benzomorphan ethylketocyclazocine (EKC) and the arylacetamide U50,488, on cocaine self-administration in rhesus monkeys. Monkeys(More)
This publication is the seventh in a series of safety evaluations performed by the Expert Panel of the Flavor and Extract Manufacturers' Association (FEMA). In 1993, the Panel initiated a comprehensive program to re-evaluate the safety of more than 1700 GRAS flavouring substances under conditions of intended use. In this review, scientific data relevant to(More)
Previously, we reported on an opioid antagonist, nor-binaltorphimine (nor-BNI), that had high selectivity for kappa opioid receptors in smooth muscle preparations. In this study, nor-BNI administered either s.c. or i.c.v. was shown to antagonize significantly the antinociceptive effects of the kappa opioid agonists, ethylketazocine and U-50,488H at doses(More)
In this study naltrindole (NTI) and its benzofuran derivative (NTB) were studied for their antagonist activity against various delta opioid receptor agonists in the tail-flick antinociceptive assay in mice. The antinociceptive ED50 of i.c.v. administered DSLET [(D-Ser2, Leu5, Thr6)enkephalin] was shifted about 4-fold by either s.c. NTB or i.c.v. NTI(More)
There has been much speculation regarding the functional relevance of G protein-coupled receptor heterodimers, primarily because demonstrating their existence in vivo has proven to be a considerable challenge. Here we show that the opioid agonist ligand 6'-guanidinonaltrindole (6'-GNTI) has the unique property of selectively activating only opioid receptor(More)
Given the mounting evidence for involvement of delta opioid receptors in the tolerance and physical dependence of mu opioid receptor agonists, we have investigated the possible physical interaction between mu and delta opioid receptors by using bivalent ligands. Based on reports of suppression of antinociceptive tolerance by the delta antagonist naltrindole(More)