Ventral subiculum administration of the somatostatin receptor agonist MK-678 increases dopamine levels in the nucleus accumbens.
Somatostatin (or somatotropin-release inhibitory factor, SRIF) binding and in situ hybridisation studies have indicated a high expression of receptor subtypes throughout the rat brain and, in particular, in subregions of the hippocampus and subiculum. In vitro, somatostatin and related peptides, including seglitide (MK-678), hyperpolarize subicular neurones of the burst firing type-a response, which may have functional consequences for their output. One major projection from the subiculum is to the nucleus accumbens. The functional consequence of somatostatin receptor stimulation in the ventral subiculum has been assessed by measuring extracellular levels of dopamine in the ipsilateral nucleus accumbens. In anaesthetised rats, administration of seglitide (MK-678), a somatostatin analogue with selectivity for the SRIF-1 receptor (comprising somatostatin sst2, sst3 and sst5 subtypes) significantly increased extracellular levels of dopamine in the ipsilateral nucleus accumbens shell. The result suggests that hyperpolarization of subicular neurones by MK-678 may lead to activation of the subiculo-accumbens projection system, and an associated increase in dopaminergic function.
Mitchell
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Lillly Research Centre, Eli Lilly and Company Ltd., Erl Wood Manor, Windlesham, Surrey, GU20 6PH, UK. mitchell_stephen@lilly.com
Sharrott
A
A
Cooper
J
J
Greenslade
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RG
D015102:3,4-Dihydroxyphenylacetic Acid / Q000378:metabolism; D000818:Animals; D004298:Dopamine / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D006719:Homovanillic Acid / Q000378:metabolism; D007031:Hypothalamus / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D009714:Nucleus Accumbens / Q000187:drug effects* / Q000378:metabolism; D010456:Peptides, Cyclic / Q000494:pharmacology*; D051381:Rats; D017481:Receptors, Somatostatin / Q000187:drug effects; D013997:Time Factors
D010456:Peptides, Cyclic; D017481:Receptors, Somatostatin; D015102:3,4-Dihydroxyphenylacetic Acid; C040968:seglitide; D004298:Dopamine; D006719:Homovanillic Acid