The effects of chronic ethanol self-administration on hippocampal 5-HT1A receptors in monkeys.
BACKGROUND
Chronic alcohol consumption reduces brain serotonin and alters the synaptic mechanisms involved in memory formation. Hippocampal 5-HT1A receptors modulate these mechanisms, but the neuroadaptive response of 5HT1A receptors to chronic alcohol self-administration is not well understood.


METHODS
Hippocampal tissue from monkeys that voluntarily self-administered ethanol for 12 months (n=9) and accompanying controls (n=8) were prepared for in vitro receptor autoradiography and laser capture microdissection. The 5-HT1A receptor antagonist, [(3)H]MPPF, and the agonist, [(3)H]8-OH-DPAT, were used to measure total and G-protein coupled 5-HT1A receptors respectively. The expression of the genes encoding the 5-HT1A receptor and its trafficking protein Yif1B was measured in microdissected dentate gyrus (DG) granule cells and CA1 pyramidal neurons.


RESULTS
An increase in G-protein coupled, but not total, receptors was observed in the posterior pyramidal cell layer of CA1 in ethanol drinkers compared to controls. Chronic ethanol self-administration was also associated with an up-regulation of total and G-protein coupled 5-HT1A receptors in the posterior DG polymorphic layer. Changes in receptor binding were not associated with concomitant changes in 5-HT1A receptor mRNA expression. Chronic ethanol self-administration was associated with a significant increase in Yif1B gene expression in posterior CA1 pyramidal neurons.


CONCLUSIONS
Chronic, ethanol self-administration up-regulates hippocampal 5-HT1A receptor density in a region-specific manner that does not appear to be due to alterations at the level of transcription but instead may be due to increased receptor trafficking. Further exploration of the mechanisms mediating chronic ethanol-induced 5-HT1A receptor up-regulation and how hippocampal neurotransmission is altered is warranted.
Neuroscience Program, Wake Forest University School of Medicine, Winston-Salem, NC, USA; Department of Physiology & Pharmacology, Wake Forest University School of Medicine, Winston-Salem, NC, USA.
Elizabeth J
EJ
Burnett
Department of Behavioral Neuroscience, Oregon Health & Science University, Portland, OR, USA.
Kathleen A
KA
Grant
Department of Physiology & Pharmacology, Wake Forest University School of Medicine, Winston-Salem, NC, USA.
April T
AT
Davenport
Neuroscience Program, Wake Forest University School of Medicine, Winston-Salem, NC, USA; Department of Physiology & Pharmacology, Wake Forest University School of Medicine, Winston-Salem, NC, USA.
Scott E
SE
Hemby
Neuroscience Program, Wake Forest University School of Medicine, Winston-Salem, NC, USA; Department of Physiology & Pharmacology, Wake Forest University School of Medicine, Winston-Salem, NC, USA. Electronic address: dfriedmn@wakehealth.edu.
David P
DP
Friedman
D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; D000437:Alcoholism / Q000235:genetics / Q000378:metabolism*; D000631:Aminopyridines / Q000378:metabolism; D000818:Animals; D001345:Autoradiography; D002492:Central Nervous System Depressants / Q000494:pharmacology*; D018076:DNA, Complementary / Q000096:biosynthesis / Q000302:isolation & purification; D000431:Ethanol / Q000494:pharmacology*; D015870:Gene Expression / Q000187:drug effects; D006624:Hippocampus / Q000187:drug effects* / Q000378:metabolism*; D006799:Housing, Animal; D008252:Macaca fascicularis; D008297:Male; D010879:Piperazines / Q000378:metabolism; D016133:Polymerase Chain Reaction; D012313:RNA / Q000096:biosynthesis / Q000302:isolation & purification; D044282:Receptor, Serotonin, 5-HT1A / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D043562:Receptors, G-Protein-Coupled / Q000187:drug effects / Q000378:metabolism; D012646:Self Administration; D012702:Serotonin Antagonists / Q000378:metabolism; D017366:Serotonin Receptor Agonists
D000631:Aminopyridines; D002492:Central Nervous System Depressants; D018076:DNA, Complementary; D010879:Piperazines; D043562:Receptors, G-Protein-Coupled; D012702:Serotonin Antagonists; D017366:Serotonin Receptor Agonists; D044282:Receptor, Serotonin, 5-HT1A; D000431:Ethanol; D012313:RNA; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; C099463:4-(2' methoxyphenyl)-1-(2'-(N-(2''-pyridinyl)-4-fluorobenzamido)ethyl)piperazine
Heaving drinking; Hippocampus; Nonhuman primate; Serotonin; Yif1B