These continuing studies of alcohol's actions on CNS neurons will determine if chronic exposure to alcohol produces long-lasting adaptive changes in cellular pathways involved in excitatory synaptic transmission. Alcohol's effects on synaptic functions that are critical to intracellular and interneuronal communication will be examined including: (a) intracellular Ca2+ signaling initiated by synaptic input, (b) neurosteroid modulation of synaptic transmission and long-term potentiation (LTP), and (c) transmitter interactions. These synaptic functions will be assessed under three conditions: (a) control baseline, (b) after chronic alcohol exposure and, (c) after a period of alcohol abstinence. A comparison of results will reveal alcohol-induced alterations in these synaptic functions and the relative permanence of the changes. Various strategies will be used to identify the cellular sites and mechanisms of alcohol action. The main transmitter to be studied is glutamate, and its actions via the NMDA receptor. Alcohol's action on opiate receptor-linked Ca2+ signaling will also be assessed. Neurons from two brain regions, the hippocampus and amygdala, will be studied. Both brain regions are known to be involved in the behavioral effects of alcohol.
The Specific Aims of the studies are: (1) to investigate effects of chronic alcohol on intracellular Ca2+ signaling events activated by synaptic input and linked to glutamate and opiate receptors, and to determine if chronic alcohol induces long-term changes in receptor-linked Ca2+ signaling pathways that are maintained during abstinence from school. (2) To determine if neurosteroid modulation of excitatory synaptic transmission and LTP is altered by alcohol treatment paradigms that produce dependence and abstinence in animal models. (3) To establish a rodent culture model of amygdala neurons for studies of alcohol's effects on synaptic systems thought to be directly involved in addictive behavior. In vitro culture and slice preparations will be used for these studies because they offer technical advantages for the electrophysiological and microscopic Ca2+ imaging techniques to be used. Results from these studies will contribute significantly to an understanding of the neuroadaptive changes induced by alcohol under conditions of alcohol dependence and abstinence, and may reveal general principles that will contribute to an understanding of the basic neuronal mechanisms underlying alcohol's actions being studied in other components of the TSRI-ARC.

Agency
National Institute of Health (NIH)
Institute
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
Type
Specialized Center (P50)
Project #
5P50AA006420-17
Application #
6299171
Study Section
Project Start
1999-12-01
Project End
2000-11-30
Budget Start
1998-10-01
Budget End
1999-09-30
Support Year
17
Fiscal Year
2000
Total Cost
$462,944
Indirect Cost
Name
Scripps Research Institute
Department
Type
DUNS #
City
La Jolla
State
CA
Country
United States
Zip Code
92037
Kononoff, Jenni; Melas, Philippe A; Kallupi, Marsida et al. (2018) Adolescent cannabinoid exposure induces irritability-like behavior and cocaine cross-sensitization without affecting the escalation of cocaine self-administration in adulthood. Sci Rep 8:13893
Verheij, Michel M M; Contet, Candice; Karel, Peter et al. (2018) Median and Dorsal Raphe Serotonergic Neurons Control Moderate Versus Compulsive Cocaine Intake. Biol Psychiatry 83:1024-1035
Takashima, Yoshio; Mandyam, Chitra D (2018) The role of hippocampal adult neurogenesis in methamphetamine addiction. Brain Plast 3:157-168
Takashima, Yoshio; Fannon, McKenzie J; Galinato, Melissa H et al. (2018) Neuroadaptations in the dentate gyrus following contextual cued reinstatement of methamphetamine seeking. Brain Struct Funct 223:2197-2211
Berger, Anthony L; Henricks, Angela M; Lugo, Janelle M et al. (2018) The Lateral Habenula Directs Coping Styles Under Conditions of Stress via Recruitment of the Endocannabinoid System. Biol Psychiatry 84:611-623
Galinato, Melissa H; Takashima, Yoshio; Fannon, McKenzie J et al. (2018) Neurogenesis during Abstinence Is Necessary for Context-Driven Methamphetamine-Related Memory. J Neurosci 38:2029-2042
Ehlers, Cindy L; Wills, Derek; Gilder, David A (2018) A history of binge drinking during adolescence is associated with poorer sleep quality in young adult Mexican Americans and American Indians. Psychopharmacology (Berl) 235:1775-1782
Serrano, Antonia; Pavon, Francisco J; Buczynski, Matthew W et al. (2018) Deficient endocannabinoid signaling in the central amygdala contributes to alcohol dependence-related anxiety-like behavior and excessive alcohol intake. Neuropsychopharmacology 43:1840-1850
Kirson, Dean; Oleata, Christopher Shaun; Parsons, Loren Howell et al. (2018) CB1 and ethanol effects on glutamatergic transmission in the central amygdala of male and female msP and Wistar rats. Addict Biol 23:676-688
Fannon, McKenzie J; Mysore, Karthik K; Williams, Jefferson et al. (2018) Hippocampal neural progenitor cells play a distinct role in fear memory retrieval in male and female CIE rats. Neuropharmacology 143:239-249

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