open field locomotion-rats
DESCRIPTION
Open Field Locomotion-Rats. Rotarod. Lever Pressing on Operant Schedules. How many times do I have to do this????. FOOD REINFORCED LEVER PRESSING: e.g. FR SCHEDULE. Elevated Plus Maze. Fig. 2.1. Radial Arm Maze. Morris Water Maze. Drug Self-administration. PHASES. - PowerPoint PPT PresentationTRANSCRIPT
Open Field Locomotion-Rats
Rotarod
FOOD REINFORCEDLEVER PRESSING: e.g. FR
SCHEDULEHow many
times do I have to do this????
Lever Pressing on Operant Schedules
Elevated Plus Maze
Fig. 2.1
Radial Arm Maze
Drug Self-administration
PHASES
Water
Lipid (a triglyceride)
Phospholipid (a diglyceride):
PhosphatidylCholineLECITHIN
Aqueous and Organic Phases
Fig. 3.1
ETHANOL MOLECULE
C
H
H
H
CH
HO
H
Lipophilic/Hydrophobic
Lipophobic/Hydrophilic
CH3CH2OH
THC Molecule
THC: High hydrocarbon content, VERYlipid soluble.
CH3H3C
H3C
H
H
O
HO (CH2)4CH3
Molecular Structure of THC(delta-9-tetrahydrocannabinol)
Routes of Administration
IC: DRUG INJECTEDDIRECTLY INTO BRAIN TISSUE
ICV: DRUG INJECTEDDIRECTLY INTO THE VENTRICLES
(fluid-filled spaces in the brain)
Typical Dose Response Curve
Dose (mg units, or mg/kg)
0 2 4 6 8 10
Res
po
nse
(f
un
ctio
nal
or
beh
avio
ral u
nit
s)
0
20
40
60
80
100
120
ED50
ED50: effective dose 50; dose thatgives 50% maximal effect; measureof POTENCY of the drug
efficacy
Structure of the Neuron
Nerve impulses (i.e., action potentials) move along the axon
Chemical signals (i.e., neurotransmitters) are released from terminals
Dendrites
Soma(cell body)
AXON
Terminals
Membrane Proteins and the Movement of Ions
Chloride channels are open
Na+ Na+ Na+
K+ K+
Na+ pump(Na+/K+ pump)Actively pumps Na+out of cell
Receptor
enzyme
SecondMessengerproduction
Fig. 4.3
EPSP, IPSP AND ACTION POTENTIAL
TIME ----->0 10 20 30 40 50 60 70
VO
LT
AG
E (
mV
)
-100
-80
-60
-40
-20
0
20
40
60
RestingMembranePotential
EPSPthreshold
ACTIONPOTENTIAL
IPSP
TRANSMITTER BINDING TO A RECEPTOR
RECEPTOR
NEUROTRANSMITTER
membrane
WHEN THE TRANSMITTER AND RECEPTOR ARE BOUND TO EACH OTHER, IT STIMULATES BIOLOGICAL ACTIVITY
Chemically GatedChannel Opens:Ions MoveInto Cell(can be EPSP or IPSP dependingon the channel)
outsideinside
Fig. 4.5
EXAMPLE OF GLUTAMATE-MEDIATED EXCITATION
RECEPTOR
GLUTAMATE
membrane
WHEN THE GLUTAMATE AND RECEPTOR ARE BOUND TO EACH OTHER, IT OPENS THE CHANNEL
Cation Channel Opens:Positive Ions Move,Na+ Ions MoveInto Cell(EPSP)
outsideinside
EXAMPLE OF GABA-MEDIATED INHIBITION
RECEPTOR
GABA
membrane
WHEN THE GABA AND RECEPTOR ARE BOUND TO EACH OTHER, IT OPENS THE CHANNEL
Cl- Channel Opens:Cl- Ions MoveInto Cell(IPSP)
outsideinside
GENERATION OF THE ACTION POTENTIAL
TIME ----->0 10 20 30 40 50 60 70
VO
LT
AG
E (
mV
)
-100
-80
-60
-40
-20
0
20
40
60
RestingMembranePotential
EPSPthreshold
ACTIONPOTENTIAL
ASCENDINGLIMB
DESCENDINGLIMB
AXON
Towardssoma
Towardsterminals
Na+
Action Potential is Generated
Na+ Na+ Na+
K+
K+ moves out-restores restingPotential (i.e., descending limb)
K+
Na+ moves in-Voltage moves more positive (ascending limb)
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.
INFORMATION PROCESSING BY NEURONS
Chemical Transmission
Calcium flowing into the terminal, which is caused by the action potential, stimulates transmitter release.
Synthesis
Storage Release
CationChannel
Postsynaptic Action (a) and Inactivation (b, c)
NEUROTRANSMITTERS AND NEUROMODULATORS
Acetylcholine
Serotonin
DA terminal
Postsynaptic cell
Synapticcleft
SYNTHESIS:Transmitter is synthesized from a precursor molecule by enzymes in the presynaptic cell
SYNAPSE: Point of functional connection
DA terminal
Postsynaptic cell
Synapticcleft
STORAGE:Transmitter is storedin presynaptic vesicles
SYNAPSE: Point of functional connection
DA terminal
Postsynaptic cell
Synapticcleft
Electrical impulse“action potential”
DA terminal
Postsynaptic cell
Synapticcleft
DA terminal
Postsynaptic cell
Synapticcleft
Ca++ RELEASE: ActionPotential opens voltage-Gated Ca++ channels
DA terminal
Postsynaptic cell
Synapticcleft
Ca++
Ca++Ca++
Ca++
RELEASE: There is aninflux of Ca++ into theterminal
DA terminal
Postsynaptic cell
Synapticcleft
.....
RELEASE:Ca++ influx promotesseveral processes thatlead the vesicles to go from a pre-release stateinto a fusion with releasesites on the membrane. Transmitter is released
.
DA terminal
Postsynaptic cell
Synapticcleft
.. ... . Transmitter
diffuses acrosssynaptic cleft...
DA terminal
Postsynaptic cell
Synapticcleft . . . .. .
Transmitterdiffuses acrosssynaptic cleft
.
.
..
DA terminal
Postsynaptic cell
Synapticcleft
. . . .. .
POSTSYNAPTICACTION:a) Transmitter bindsto postsynapticreceptors
DA Receptor proteins
...
DA terminal
Postsynaptic cell
Synapticcleft
Physiological and biochemical effects (EPSPs
or IPSPs)
POSTSYNAPTIC ACTION:b) Transmitter bindinginduces intrinsic biologicalactivity (i.e. signaltransduction effects) inpostsynaptic cell.
.
..
Typical Dose Response Curve
Dose (mg units, or mg/kg)
0 2 4 6 8 10
Res
po
nse
(f
un
ctio
nal
or
beh
avio
ral u
nit
s)
0
20
40
60
80
100
120
Kd
Kd or IC50: concentration thatgives 50% maximal binding; measure
of AFFINITY of the drug for the receptor
MaximumNumber ofreceptors
Concentration of Drug Used
TYPICAL BINDING CURVE
SP
EC
IFIC
BIN
DIN
G(N
UM
BE
R O
F R
EC
EP
TO
RS
OC
CU
PIE
D)
LIGAND BINDING TO A RECEPTOR
RECEPTOR
LIGAND
membrane
+
+-
-
WHEN THE LIGAND AND RECEPTOR ARE BOUND TO EACH OTHER, IT STIMULATES THE INTRINSIC BIOLOGICAL ACTIVITY (i.e., signal transduction)
Signaltransductionmechanism
outsideinside
IONOTROPIC SIGNAL TRANSDUCTION
RECEPTOR
NEUROTRANSMITTER
membrane
WHEN THE TRANSMITTER AND RECEPTOR ARE BOUND TO EACH OTHER, IT STIMULATES BIOLOGICAL ACTIVITY
Chemically GatedChannel Opens:Ions MoveInto Cell(can be EPSP or IPSP dependingon the channel)
outsideinside
EXAMPLES: GLUTAMATE ANDGABA MECHANISMS THAT OPENCATION OR Cl- CHANNELS
METABOTROPIC SIGNAL TRANSDUCTION
RECEPTOR
NEUROTRANSMITTER
membrane
WHEN THE TRANSMITTER AND RECEPTOR ARE BOUND TO EACH OTHER, IT STIMULATES BIOLOGICAL ACTIVITY
G-proteins activated:Regulates enzymes;leads to productionof 2nd messengers(e.g. c-AMP, IP3)(can be EPSP or IPSP depending on the processes affected)
outsideinside
EXAMPLES: DA acting on D1 receptors increases c-AMP production.
Fig. 5.5
Multiple Receptor Subtypes
• Each transmitter generally has more than 1 receptor
• These are called “subtypes”
D1Family
D2Family
Multiple Locations for ReceptorsPresynaptic terminal
Postsynaptic cell
Synapticcleft
PresynapticReceptors
PostsynapticReceptors
Fig. 4.7
AGONISTS: BINDING AND SIGNAL TRANSDUCTION
RECEPTOR
AGONIST
membrane
+
+-
-
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.
Signaltransductionmechanism
outsideinside
COMPETITIVE ANTAGONISTS:BINDING AND SIGNAL TRANSDUCTION
RECEPTOR
ANTAGONIST OCCUPIES RECEPTOR;THIS BLOCKS THE NEUROTRANSMITTEROR AGONIST FROM BINDING
membrane
+
+-
-
ANTAGONIST AND RECEPTOR ARE IN THEBOUND STATE
outsideinside
NEUROTRANSMITTERIS DISPLACED FROMTHE RECEPTOR
INVERSE AGONISTS:BINDING AND SIGNAL TRANSDUCTION
RECEPTOR
LIGAND
membrane
+
+-
-
WHEN THE INVERSE AGONISTAND RECEPTOR ARE BOUND TO EACH OTHER, IT STIMULATES THE OPPOSITEINTRINSIC BIOLOGICAL ACTIVITY (i.e., signal transduction effects opposite from those produced by the neurotransmitter)
Signaltransductionmechanism
outsideinside
DRUGS THAT AFFECT POSTSYNAPTIC MECHANISMS BY ACTIONS ON SITES
OTHER THAN THE BINDING SITE
- NONCOMPETITIVE ANTAGONISTS
Competitive GABAantagonists act here
Noncompetitive GABAantagonist acts here; block the channel
Fig. 10.3
DRUGS THAT AFFECT POSTSYNAPTIC MECHANISMS BY ACTIONS ON SITES
OTHER THAN THE BINDING SITE
- POSITIVE ALLOSTERIC MODULATORS
Benzodiazepines likeValium are positiveallosteric modulatorsthat act here
Fig. 10.3
POSTSYNAPTIC ACTION: AN IMPORTANT SITE OF DRUG
INTERACTIONS• There are interactions between agonists and
antagonists that act on the same receptor
Fig. 5.7
POSTSYNAPTIC ACTION: AN IMPORTANT SITE OF DRUG
INTERACTIONS
• There are interactions between drugs that act on different receptors, but ultimately these actions converge on to the same signal transduction mechanisms
C-AMPC-AMP
D2
A2A
STRIATUM(in the forebrain)
-
+
GABA
STRIATAL NEURONS: Neurons originating in brain area involved in PD symptoms
DA D2 antagonism increases c-AMP
DA D2 stimulation decreases c-AMP
Adenosine A2A stimulation increases c-AMP
Adenosine A2A antagonism decreases c-AMP
Presynaptic terminal
Postsynaptic cell
Synapticcleft
Inactivation.Transmitter is brokendown (i.e.
“metabolized”)by enzymes.
..
Presynaptic terminal
Postsynaptic cell
Synapticcleft
Inactivation.Transmitter is
transported back into presynaptic terminal by protein transporter (i.e., uptake or “reuptake”).
...
Neuromuscular Junction
Neuromuscular Junction:
Acetylcholine (ACH) is the neurotransmitter.ACh release makes muscle fibers contract.
Motor Neuron
Striated(“voluntary”)muscle {
NicotinicAChReceptors onMuscle Fibers
AutonomicNervousSystem
Sympathetic and Parasympathetic Divisions are shown.
Sympathetic: NE is neurotransmitter. Promotes energy expenditure, activated by emotion
and stress (e.g. increases heart rate, blood pressure, decreases
lung secretions)
Parasympathetic: ACH is neurotransmitter. Promotes
digestion and excretion (e.g., decreases heart rate & blood
pressure, stimulates salivation, lung secretions, stomach and
intestinal activity)
NE ACH
Major Divisions of Brain
anterior posterior
FOREBRAIN
MIDBRAINHINDBRAIN
Major Divisions of Brain
FOREBRAIN
MIDBRAINHINDBRAIN
Brain Anatomy
hippocampus
cerebellum
neocortex
Prefrontalcortex
Cingulatecortex
Caudate/putamen
Nucleusaccumbens
Basalforebrain
hypothalamus
Substantianigra Ventral
Tegmentalarea
Raphe
Locusceruleusthalamus pons
medulla
amygdala
Brain Anatomy: DA
hippocampus
cerebellum
neocortex
Prefrontalcortex
Cingulatecortex
Caudate/putamen
Nucleusaccumbens
Basalforebrain
hypothalamus
SubstantiaNigra(SNc)
VentralTegmentalArea(VTA)
Raphe
Locusceruleusthalamus
amygdala
see Fig. 5.10
Brain Anatomy: ACh
hippocampus
cerebellum
neocortex
Prefrontalcortex
Cingulatecortex
Caudate/putamen
Nucleusaccumbens
Basalforebrain
hypothalamus
Substantianigra Ventral
Tegmentalarea
Raphe
Locusceruleusthalamus
amygdala
see Fig. 5.10
Brain Anatomy: NE
hippocampus
cerebellum
neocortex
Prefrontalcortex
Cingulatecortex
Caudate/putamen
Nucleusaccumbens
Basalforebrain
hypothalamus
Substantianigra Ventral
Tegmentalarea
Raphe
Locusceruleusthalamus
amygdala
see Fig. 5.11
Brain Anatomy: Serotonin (5-HT)
hippocampus
cerebellum
neocortex
Prefrontalcortex
Cingulatecortex
Caudate/putamen
Nucleusaccumbens
Basalforebrain
hypothalamus
Substantianigra Ventral
Tegmentalarea
Raphe
Locusceruleusthalamus
amygdala
see Fig. 5.11