The long term goal of the proposed research is to generate guiding principles for interpretation of the role of telencephalic opioid peptides in brain and behavioral mechanisms. Efforts toward this understanding involve the effects of convulsant and psychoactive drugs on the structure and function of identified opioid peptidergic pathways in the cerebral cortex, hippocampal formation, and basal ganglia of rats. First, in adult and developing rats, immunohistochemistry and in situ hybridization histochemistry will be used to determine the similarities and distinctions between the telencephalic neuronal systems containing prodynorphin and/or proenkephalin. Opioid peptide immunocytochemistry will be combined with immunostaining of Substance P and glutamic acid decarboxylase in order to determine possible colocalization of these substances with the opioids in overlapping forebrain systems. Second, regulation of the expression of opioid peptides in identified pathways will be explored in hippocampal transplants and in normal limbic cortex. A third series of experiments is based on the recently demonstrated ability of the dopamirergic agonist, apomorphine, to increase the synthesis of dynorphin and substance P in striatonigral neurons. To explore the hypothesis that the apomorphine effect is mediated by cholinergic activity, administration of a cholinergic agonist and antagonist will be combined with repeated apomorphine injections in an attempt to modify the apomorphine-induced increase in striatal dynorphin and Substance P. Immunocytochemistry and in situ hybridization histochemistry will be employed to determine alterations in the biosynthesis of telencephalic opioid peptides at the cellular lever. With the combined use of immunochemical and molecular neurobiological tools, these studies will continue the efforts to define the functional organization and drug-induced metabolic responsiveness of the telencephalic systems which certain opioid peptides.

Agency
National Institute of Health (NIH)
Institute
National Institute on Drug Abuse (NIDA)
Type
Research Project (R01)
Project #
5R01DA003982-07
Application #
3208899
Study Section
Drug Abuse Biomedical Research Review Committee (DABR)
Project Start
1988-05-01
Project End
1991-11-30
Budget Start
1990-02-01
Budget End
1990-11-30
Support Year
7
Fiscal Year
1990
Total Cost
Indirect Cost
Name
East Carolina University
Department
Type
Schools of Medicine
DUNS #
City
Greenville
State
NC
Country
United States
Zip Code
27858
Schmidt, Heath D; McGinty, Jacqueline F; West, Anne E et al. (2013) Epigenetics and psychostimulant addiction. Cold Spring Harb Perspect Med 3:a012047
Schwendt, Marek; Sigmon, Stacey A; McGinty, Jacqueline F (2012) RGS4 overexpression in the rat dorsal striatum modulates mGluR5- and amphetamine-mediated behavior and signaling. Psychopharmacology (Berl) 221:621-35
Shi, Xiangdang; McGinty, Jacqueline F (2011) D1 and D2 dopamine receptors differentially mediate the activation of phosphoproteins in the striatum of amphetamine-sensitized rats. Psychopharmacology (Berl) 214:653-63
McGinty, Jacqueline F; Bache, Alexandra J; Coleman, Nortorious T et al. (2011) The Role of BDNF/TrkB Signaling in Acute Amphetamine-Induced Locomotor Activity and Opioid Peptide Gene Expression in the Rat Dorsal Striatum. Front Syst Neurosci 5:60
Schwendt, M; McGinty, J F (2010) Amphetamine up-regulates activator of G-protein signaling 1 mRNA and protein levels in rat frontal cortex: the role of dopamine and glucocorticoid receptors. Neuroscience 168:96-107
Saylor, Alicia J; McGinty, Jacqueline F (2010) An intrastriatal brain-derived neurotrophic factor infusion restores striatal gene expression in Bdnf heterozygous mice. Brain Struct Funct 215:97-104
McGinty, Jacqueline F; Whitfield Jr, Timothy W; Berglind, William J (2010) Brain-derived neurotrophic factor and cocaine addiction. Brain Res 1314:183-93
Saylor, A J; McGinty, J F (2008) Amphetamine-induced locomotion and gene expression are altered in BDNF heterozygous mice. Genes Brain Behav 7:906-14
McGinty, Jacqueline F; Shi, Xiangdang D; Schwendt, Marek et al. (2008) Regulation of psychostimulant-induced signaling and gene expression in the striatum. J Neurochem 104:1440-9
Boger, Heather A; Middaugh, Lawrence D; Patrick, Kennerly S et al. (2007) Long-term consequences of methamphetamine exposure in young adults are exacerbated in glial cell line-derived neurotrophic factor heterozygous mice. J Neurosci 27:8816-25

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