Open Field Locomotion-Rats

1. Open Field Locomotion-Rats

3. Rotarod

4. Lever Pressing on Operant Schedules How many times do I have to do this???? FOOD REINFORCED LEVER PRESSING: e.g. FR SCHEDULE

5. Elevated Plus Maze Fig. 2.1

6. Radial Arm Maze

7. Morris Water Maze

8. Drug Self-administration

9. PHASES Lipid (a triglyceride) Water Phospholipid (a diglyceride): Phosphatidyl Choline LECITHIN

10. Aqueous and Organic Phases Fig. 3.1

11. H H H C C H H O H ETHANOL MOLECULE Lipophilic/Hydrophobic Lipophobic/ Hydrophilic CH3CH2OH

12. (CH2)4CH3 HO H H3C O H CH3 H3C THC Molecule Molecular Structure of THC (delta-9-tetrahydrocannabinol) THC: High hydrocarbon content, VERY lipid soluble.

13. Routes of Administration IC: DRUG INJECTED DIRECTLY INTO BRAIN TISSUE ICV: DRUG INJECTED DIRECTLY INTO THE VENTRICLES (fluid-filled spaces in the brain)

14. efficacy ED50 ED50: effective dose 50; dose that gives 50% maximal effect; measure of POTENCY of the drug

15. Structure of the Neuron Chemical signals (i.e., neurotransmitters) are released from terminals Dendrites Terminals Nerve impulses (i.e., action potentials) move along the axon Soma (cell body) AXON

16. Membrane Proteins and the Movement of Ions Na+ pump (Na+/K+ pump) Actively pumps Na+ out of cell Na+ Na+ Na+ Receptor K+ K+ enzyme Chloride channels are open Second Messenger production Fig. 4.3

17. EPSP, IPSP AND ACTION POTENTIAL ACTION POTENTIAL EPSP threshold Resting Membrane Potential IPSP

18. outside inside WHEN THE TRANSMITTER AND RECEPTOR ARE BOUND TO EACH OTHER, IT STIMULATES BIOLOGICAL ACTIVITY RECEPTOR Chemically Gated Channel Opens: Ions Move Into Cell (can be EPSP or IPSP depending on the channel) NEUROTRANSMITTER membrane TRANSMITTER BINDING TO A RECEPTOR

19. Fig. 4.5

20. EXAMPLE OF GLUTAMATE-MEDIATED EXCITATION outside inside WHEN THE GLUTAMATE AND RECEPTOR ARE BOUND TO EACH OTHER, IT OPENS THE CHANNEL RECEPTOR Cation Channel Opens: Positive Ions Move, Na+ Ions Move Into Cell (EPSP) GLUTAMATE membrane

21. EXAMPLE OF GABA-MEDIATED INHIBITION outside inside WHEN THE GABA AND RECEPTOR ARE BOUND TO EACH OTHER, IT OPENS THE CHANNEL RECEPTOR Cl- Channel Opens: Cl- Ions Move Into Cell (IPSP) GABA membrane

22. GENERATION OF THE ACTION POTENTIAL ACTION POTENTIAL DESCENDING LIMB ASCENDING LIMB EPSP threshold Resting Membrane Potential

23. Action Potential is Generated Na+ moves in- Voltage moves more positive (ascending limb) K+ Na+ Na+ Na+ Na+ K+ K+ moves out- restores resting Potential (i.e., descending limb) AXON Towards terminals Towards soma

24. INFORMATION PROCESSING BY NEURONS Each neuron is like a tiny computer; it receives many inputs, both excitatory and inhibitory, and adds them together (i.e. summation) over time and space. If the summed excitatory input at the initial part of the axon exceeds the threshold, an action potential is fired.

25. Chemical Transmission Synthesis Storage Release Cation Channel Calcium flowing into the terminal, which is caused by the action potential, stimulates transmitter release.

26. Postsynaptic Action (a) and Inactivation (b, c)

27. NEUROTRANSMITTERS AND NEUROMODULATORS Serotonin Acetylcholine

28. SYNAPSE: Point of functional connection DA terminal SYNTHESIS: Transmitter is synthesized from a precursor molecule by enzymes in the presynaptic cell Synaptic cleft Postsynaptic cell

29. SYNAPSE: Point of functional connection DA terminal STORAGE: Transmitter is stored in presynaptic vesicles Synaptic cleft Postsynaptic cell

30. Electrical impulse “action potential” DA terminal Synaptic cleft Postsynaptic cell

31. DA terminal Synaptic cleft Postsynaptic cell

32. DA terminal Ca++ RELEASE: Action Potential opens voltage- Gated Ca++ channels Synaptic cleft Postsynaptic cell

33. DA terminal Ca++ Ca++ Ca++ Ca++ RELEASE: There is an influx of Ca++ into the terminal Synaptic cleft Postsynaptic cell

34. DA terminal RELEASE: Ca++ influx promotes several processes that lead the vesicles to go from a pre-release state into a fusion with release sites on the membrane. Transmitter is released . . . . . . Synaptic cleft Postsynaptic cell

35. DA terminal . Transmitter diffuses across synaptic cleft . . . . . . Synaptic cleft . . Postsynaptic cell

36. DA terminal Transmitter diffuses across synaptic cleft . Synaptic cleft . . . . . . . . . Postsynaptic cell

37. DA terminal POSTSYNAPTIC ACTION: a) Transmitter binds to postsynaptic receptors . Synaptic cleft . . . . . . . . DA Receptor proteins Postsynaptic cell

38. DA terminal POSTSYNAPTIC ACTION: b) Transmitter binding induces intrinsic biological activity (i.e. signal transduction effects) in postsynaptic cell. . . Synaptic cleft . Physiological and biochemical effects (EPSPs or IPSPs) Postsynaptic cell

39. TYPICAL BINDING CURVE Maximum Number of receptors SPECIFIC BINDING (NUMBER OF RECEPTORS OCCUPIED) Kd Concentration of Drug Used Kd or IC50: concentration that gives 50% maximal binding; measure of AFFINITY of the drug for the receptor

40. LIGAND BINDING TO A RECEPTOR outside inside WHEN THE LIGAND AND RECEPTOR ARE BOUND TO EACH OTHER, IT STIMULATES THE INTRINSIC BIOLOGICAL ACTIVITY (i.e., signal transduction) RECEPTOR - + - + Signal transduction mechanism LIGAND membrane

41. outside inside WHEN THE TRANSMITTER AND RECEPTOR ARE BOUND TO EACH OTHER, IT STIMULATES BIOLOGICAL ACTIVITY RECEPTOR Chemically Gated Channel Opens: Ions Move Into Cell (can be EPSP or IPSP depending on the channel) NEUROTRANSMITTER membrane IONOTROPIC SIGNAL TRANSDUCTION EXAMPLES: GLUTAMATE AND GABA MECHANISMS THAT OPEN CATION OR Cl- CHANNELS

42. outside inside WHEN THE TRANSMITTER AND RECEPTOR ARE BOUND TO EACH OTHER, IT STIMULATES BIOLOGICAL ACTIVITY RECEPTOR NEUROTRANSMITTER G-proteins activated: Regulates enzymes; leads to production of 2nd messengers (e.g. c-AMP, IP3) (can be EPSP or IPSP depending on the processes affected) membrane METABOTROPIC SIGNAL TRANSDUCTION EXAMPLES: DA acting on D1 receptors increases c-AMP production.

43. Fig. 5.5

44. Multiple Receptor Subtypes • Each transmitter generally has more than 1 receptor • These are called “subtypes” D1 Family D2 Family

45. Presynaptic terminal Synaptic cleft Postsynaptic cell Multiple Locations for Receptors Presynaptic Receptors Postsynaptic Receptors Fig. 4.7

46. AGONISTS: BINDING AND SIGNAL TRANSDUCTION outside inside WHEN THE AGONIST AND RECEPTOR ARE BOUND TO EACH OTHER, IT STIMULATES THE SAME INTRINSIC BIOLOGICAL ACTIVITY (i.e., signal transduction) AS THE TRANSMITTER ITSELF. RECEPTOR - + - + Signal transduction mechanism AGONIST membrane

47. COMPETITIVE ANTAGONISTS: BINDING AND SIGNAL TRANSDUCTION outside inside ANTAGONIST AND RECEPTOR ARE IN THE BOUND STATE RECEPTOR - + NEUROTRANSMITTER IS DISPLACED FROM THE RECEPTOR - + ANTAGONIST OCCUPIES RECEPTOR; THIS BLOCKS THE NEUROTRANSMITTER OR AGONIST FROM BINDING membrane

48. INVERSE AGONISTS: BINDING AND SIGNAL TRANSDUCTION outside inside WHEN THE INVERSE AGONIST AND RECEPTOR ARE BOUND TO EACH OTHER, IT STIMULATES THE OPPOSITE INTRINSIC BIOLOGICAL ACTIVITY (i.e., signal transduction effects opposite from those produced by the neurotransmitter) RECEPTOR - + - + Signal transduction mechanism LIGAND membrane

49. DRUGS THAT AFFECT POSTSYNAPTIC MECHANISMS BY ACTIONS ON SITES OTHER THAN THE BINDING SITE - NONCOMPETITIVE ANTAGONISTS Competitive GABA antagonists act here Noncompetitive GABA antagonist acts here; block the channel Fig. 10.3

50. DRUGS THAT AFFECT POSTSYNAPTIC MECHANISMS BY ACTIONS ON SITES OTHER THAN THE BINDING SITE - POSITIVE ALLOSTERIC MODULATORS Benzodiazepines like Valium are positive allosteric modulators that act here Fig. 10.3