Pindolol‐insensitive [³H]‐5‐hydroxytryptamine binding in the rat hypothalamus; identity with 5‐hydroxytryptamine₇ receptors

Abstract

1 Pindolol-insensitive [ 3 H]-5-hydroxytryptamine ([ 3 H]-5-HT) binding to rat hypothalamic membranes was pharmacologically and functionally characterized to resolve whether this procedure selectively labels 5-HT 7 receptors. 2 Consistent with a previous report, 3 mM and not 100 nM pindolol was required to occupy fully 5-HT 1A and 5-HT 1B receptors. Remaining

Selective serotonin receptor stimulation of the medial nucleus accumbens causes differential effects on food intake and locomotion.

“…Few previous reports have examined the role of central 5-HT 7 receptors on food intake or food-directed motivation. Knockdown of hypothalamic 5-HT 7 receptors by intracerebroventricular injections of antisense oligonucleotides does not selectively reduce feeding or locomotor activity (Clemett, Cockett, Marsden, & Fone, 1998), and systemic blockade of these receptors (along with those of D2, 5-HT 1A , and sigma receptors) by tiospirone only influence lever-pressing for food reward at levels that also induce catatonia (Arolfo & McMillen, 1999). However, in these experiments, stimulation of nucleus accumbens 5-HT 1/7 receptors with the drug 5-CT reduced feeding in rats in a dose-dependent manner.…”

Characterization of SB‐269970‐A, a selective 5‐HT7 receptor antagonist

“…In brain tissue from various species, 5‐HT 7 receptor mRNA is discretely localized within thalamus, hypothalamus, limbic and cortical regions ( Ruat et al ., 1993 , Bard et al ., 1993 , To et al ., 1995 ). Neurochemical lesioning studies indicate that, at least in the hypothalamus, they are located post‐synaptically ( Clemett et al ., 1999 ). 5‐HT 7 receptor mRNA is also present in smooth muscle cells from human, porcine and rat blood vessels ( Bard et al ., 1993 , Schoeffter et al ., 1996 ) and has been reported in human gastrointestinal tract ( Bard et al ., 1993 ) and rat lumbar dorsal root and sympathetic ganglia ( Meuser & Pierce, 1997 ).…”

[3H]‐SB‐269970 – A selective antagonist radioligand for 5‐HT7 receptors

“…The majority of radioligand binding studies to characterize 5‐HT 7 receptors in recombinant and native tissue systems have used the agonist radioligands [ 3 H]‐5‐HT ( Bard et al ., 1993 ; Tsou et al ., 1994 ; Sleight et al ., 1995 ; Clemett et al ., 1999a ) or [ 3 H]‐5‐CT ( To et al ., 1995 ; Boyland et al ., 1996 ; Thomas et al ., 1998 ; Stowe & Barnes, 1998 ; Thomas et al ., 1999 , 1999 ). These radioligands have proved useful in characterizing the pharmacological profile of cloned and native 5‐HT 7 receptors, as well as providing information on their native tissue distribution, particularly in brain.…”