Acute amygdalar activation induces an upregulation of multiple monoamine G protein coupled pathways in rat hippocampus.

Benes FM, Burke RE, Walsh J, Berretta S, Matzilevich D, Minns M, Konradi C
Mol Psychiatry. 2004 9 (10): 932-45, 895

PMID: 15170462 · DOI:10.1038/sj.mp.4001524

A "partial" rodent model for schizophrenia has been used to characterize the regulation of hippocampal genes in response to amygdalar activation. At 96 h after the administration of picrotoxin into the basolateral nucleus, we have observed an increase in the expression of genes associated with 18 different monoamine (ie adrenergic alpha 1, alpha 2 and beta 2, serotonergic 5HT5b and 5HT6, dopamine D4 and muscarinic m1, m2 and m3) and peptide (CCK A and B, angiotensin 1A, mu and kappa opiate, FSH, TSH, LH, GNRH, and neuropeptide Y) G-protein coupled receptors (GPCRs). These latter receptors are associated with three different G protein signaling pathways (Gq, Gs, and Gi) in which significant changes in gene expression were also noted for adenylate cyclase (AC4), phosphodiesterase (PDE4D), protein kinase A (PKA), and protein kinase C (PKC). Quantitative RT-PCR was used to validate the results and demonstrated that there were predictable increases of three GPCRs selected for this analysis, including the dopamine D4, alpha 1b, and CCK-B receptors. Eight out of the nine monoamine receptors showing these changes have moderate to high affinity for the atypical antipsychotic, clozapine. Taken together, these results suggest that amygdalar activation may play a role in the pathophysiology and treatment of psychosis by regulating the activity of multiple GPCR and metabolic pathways in hippocampal cells.

MeSH Terms (20)

Amygdala Animals Biogenic Monoamines Disease Models, Animal Fluorescence Resonance Energy Transfer Gene Expression Profiling Gene Expression Regulation GTP-Binding Proteins Hippocampus Injections Male Oligonucleotide Array Sequence Analysis Picrotoxin Rats Rats, Sprague-Dawley Receptors, G-Protein-Coupled Receptors, Neurotransmitter Reverse Transcriptase Polymerase Chain Reaction RNA, Messenger Schizophrenia

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