Transcript Carol Dwan
The effects of benzodiazepine inverse-agonist RY-10 on learning in a new olfactory apparatus By Carol Dwan Advisor: Mark Galizio The GABA receptor • GABA (gamma-aminobutyric acid) is the most common inhibitory neurotransmitter in the brain. When this molecule binds to it’s receptor it makes the neuron less likely to fire. • Complex molecule with multiple receptor sites The GABA receptor Benzodiazepines • Are one class of molecules that bind to GABA receptor and change it’s affinity for GABA. benzodiazepine Chloride channel Benzodiazepine drug actions • Agonist: Increases the affinity of the receptor for GABA: produces inhibitory effects in the brain. – Anxiolytic, sedative, anterograde amnesia – Often used for sleeping pills, surgical anesthetics • Antagonist: Blocks the benzodiazepine site so that agonists can not bind. • Inverse-agonist: Binds to the benzodiazepine site, decreases receptor affinity for GABA: causes the opposite effects of agonists – procovulsant, anxiogenic and mnemonic enhancing. Selective Mnemonic Enhancement • There are several subtypes of GABA receptors throughout the brain. • The GABA a5 receptor is located primarily in the hippocampus, a memory center in the brain. • RY-10 binds selectively to this receptor, and so exerts its inverse-agonist effects mainly in the memory center….with less activity in motor or cognitive centers. The Brain Goal • To test 6 rats on 4 doses (0,1,3,10 mg/kg) of RY-10 in a RAP procedure in a new olfactory apparatus. Apparatus Spices and spice cups Pellet dispensers Performance Component 1. 2. 3. 4. 5. Door 1 Door 2 Door 3 Parsley(+) Sage Parsley(+) Rosemary Rosemary Sage Rosemary Rosemary Sage Parsley(+) Rosemary Parsley(+) Sage Parsley(+) Sage Acquisition Component: • Day 1: Garlic Clove Nutmeg(+) • Day 2: Anise Caraway Cinnamon(+) • Day 3: nutmeg cinnamon mustard (+) Data Analysis • I will perform a 2x4 ANOVA statistical analysis looking for an interaction between dose and component. If the drug does not have a selective effect on learning there will be a main effect of dose. • Data will be analyzed graphically Effect on learning and performance (non selective) 7 6 5 4 performance acquisition 3 2 1 0 saline 0 1 3 10 Both elements show improvement Selective effect 7 6 5 4 performance acquisition 3 2 1 0 saline 0 1 3 10 Possible benefits • Recent testing of RY-10 did seem to show only mnemonic enhancing effects (no motor side effects) but did not properly control for confounds. (follow up on Delorey’s study) • This project is in collaboration with University of Wisconsin chemist James Cook and Harvard primate researcher James Rowlett. Compound designed for selective binding, could have novel behavioral effects. • Apparatus ceiling effects prevented The End • Questions?