Dissertation Proposal

The Effects of Ethanol and Ethanol Metabolites on Locomotor Activation and Ataxia: Focus on the Substantia Nigra pars Reticulata Maria Arizzi, M.A. Dissertation Proposal

Biphasic Effects ,[object Object],[object Object]

Biphasic Effect in Mice and Humans ,[object Object],[object Object],[object Object],[object Object],[object Object]

Biphasic Effects in Rats ,[object Object],[object Object]

Effects of Ethanol, Acetaldehyde, and Acetate on Locomotor Activity in Rats: Open Field

Ethanol infused into lateral ventricles: locomotor activity First 10 minutes stabilimeter

Peripheral Metabolism Ethanol Acetaldehyde Acetate ADH, CYP 450, CAT ALDH

Brain Metabolism Ethanol Acetaldehyde Acetate CAT ALDH

0 20 40 60 80 100 120 ACETALDEHYDE DOSE (  mol) ** ** * MOTOR ACTIVITY (counts in 10 minutes ) ETHANOL DOSE (  mol ) Ethanol and Acetaldehyde infused in to the lateral ventricles: First 10 minutes, stabilimeter 0 0.7 1.4 2.8

Working Hypotheses ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]

What are the brain areas that mediate the activating effects of ethanol and acetaldehyde?

[object Object],[object Object],[object Object],[object Object]

SNr and Motor Behavior ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]

SNr STRIATUM STN Superior Colliculus Reticular Formation Brainstem Motor Motor Thalamus

SNr, GABA, and Motor Behavior ,[object Object],[object Object],[object Object],Trevitt et al. 2002

Ethanol and GABA ,[object Object],[object Object]

Why SNr? ,[object Object],[object Object],[object Object],[object Object]

List of Experiments Acetate Ataxia Experiment 9 Acetaldehyde Ataxia Experiment 8 Ethanol Ataxia Experiment 7 Acetaldehyde, sodium azide Locomotor Activity Experiment 6 Ethanol, sodium azide Locomotor Activity Experiment 5 Acetate Locomotor Activity Experiment 4 Acetaldehyde Locomotor Activity Experiment 3 Ethanol, dorsal site Locomotor Activity Experiment 2 Ethanol Locomotor Activity Experiment 1 Drug Task Experiment

Sedation Scale ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],Salamone et al. 1996

Hypotheses ,[object Object],[object Object],[object Object]

Hypotheses (continued) ,[object Object]

Hypotheses (continued) ,[object Object],[object Object],[object Object]

[object Object],GABA. Like benzodiazepines, barbiturates and anesthetics, acute ethanol enhances GABA’s influence on GABA A receptor thus facilitating Cl- influx. (10-50 mM). This process seems to be mediated by the phosphorylation induced by PKC (protein kinase C). Chronic ethanol administration produces the opposite effects on GABA A receptors and reduces the synthesis of one of protein subunits of this receptor. Glutamate. Acute administration inhibits NMDA receptor/cation channel complex (20-50 mM). This inhibition interferes with excitotoxicity in cortex, and with LTP in the hippocampus. Chronic administration increases NMDA receptor numbers.

DA. Acute and Chronic alcohol administration induces dopamine release in the N. Accumbens. 5-HT. Acute ethanol induces the release of serotonin and facilitates the cation-5-HT 3 -gated channel (10-50 mM). Chronic alcohol increases the number of 5-HT 2. ,[object Object]

Endogenous Opioids . Acute alcohol increases endorphin and enkephalin expression and release. Chronic alcohol produces the opposite effects. Adenosine . Acute alcohol increases extracellular adenosine by inhibiting adenosine uptake, and increases synthesis of adenosine. The activation of the A 2 receptor increases intracellular cAMP. Chronic alcohol produces the opposite effects. ,[object Object]

Evidence of central ethanol metabolism by Catalase. ,[object Object],[object Object],[object Object],[object Object]

Dissertation Proposal

Recommended

Recommended

More Related Content

Similar to Dissertation Proposal

Similar to Dissertation Proposal (20)

Dissertation Proposal