Neuropharm and neurosci Flashcards
define neuropharmocology:
- study function of neurons, systems that they drive
- not only applied to neurons in brain, also neurons leading to peripheral control of organs/mm
define pharmacology:
- drug interaction w receptors/ binding sites
- effect on brain and body
NT release: procedure
- NT exists in presyn, released (exocytosis)
- release of AP
- acts on receptor (biological effect)
- inactivation (unbound NT transported into presyn terminal) reuptake= endocytosis
- application of exogenous chemical (agonist or antagonist of NT)
receptor activation: ionotropic receptors
- ligand gated ion channels
- composed 5 subunits
- binding of NT to subunit, causing to move and create channel
- +ve and -ve ions flow into cell
receptor activation: metabotropic receptors mechanism
- activate ion channels/ 2º messenger system
- need metabolic process through G protein to cause effect
- receptor binds activating G protein, GDP replaced w GTP
- G protein splits, activates effector proteins - 2º messenger systems or ion channels
define: agonist
- direct communication
- binds to receptor, effect of neuron
- works like NT
define: antagonist
- direct communication
- binds to receptor but not effect of neuron
- stops NT from having effect
define: positive allosteric modulator (PAM)
- enhances function of agonists at receptor
define: negative allosteric modulator (NAM)
- reduces function of agonist at receptor
we use neuropharm to: list (4)
- investigate how NT interact within particular circuits in the brain
- determine how peripheral neurons work, what brain regions/ NT drive them
- understand how NT/ neuropeptides work in brain to drive behaviour
- drive hormone release by brain structures/ NT
hormone release: list glands (2)
- pineal
- pituitary
hormone release: pineal hormone
- melatonin
hormone release: pituitary reg by? (region)
- regulated by hypothalamus
hormone release: ant pituitary controlled by
- parvocellular secretory cells of hypothalamus
hormone release: ant pituitary releases (6)
- ACTH
- FSH
- LH
- TH
- GH
- prolactin
hormone release: list post pituitary hormones (2)
- vasopressin
- oxytocin
hormone release: oxytocin reg by, released where?
- magnocellular neurosecretory cells of hypothalamus
- released into blood vessels of post lobe of pituitary gland
hormone release: oxytocin periphery regulates (3)
- myometrial contractions (contracts uterus during childbirth)
- contracts myoepithelial cells in mammary glands for milk expression (breastfeeding/ lactation)
- increases sperm no. and contractions needed for ejaculation
oxytocin: effects in brain (5)
social neuropeptide:
- social interactions btw peers
- formation of monogamous pair bonding
- sexual arousal and orgasm
- maternal behaviour
- social memory and anxiety reduction (anxiolytic)
oxytocin (OXY): location in the brain
- magnocellular neurosecretory cells of hypothalamus
- magnocellular cells are in PVN (paraventricular nucleus), SON (supraoptic nucleus) and accessory nucleus of hypothalamus
oxytocin: SON- function and spread
- mostly volume transmission and neuron to neuron contact
oxytocin: PVN- function and travels to
- classical neuron to neuron contact and vol transmission (less than in SON)
- oxytocin receptors in brain aka OT receptors
pharmacology of amphetamines: function
- increase extracellular monoamines
- reverse monoamine and vesicular transporters (VMAT)
- methamphetamine reverses DAT, VMAT
pharmacology of amphetamines: eg. ecstacy
- type of amphetamine
- reverses SERT (serotonin transporter)
oxytocin (OXY) in METH taking and relapse: summary (2)
- oxytocin reduced motivation to consume methamphetamine
- reduced relapse to meth-seeking behaviour
where in brain is oxytocin inhibiting behavioural effects of meth?
c-fos: function
- immediate early gene
- neurons activated, gene upregulated
- increase in manufacture of protein c-Fos
- c-Fos immunohistochemistry labels excited cells in brain
OXY: brain regions affected (2)
- nucleus accumbens (NAc)
- subthalamic nucleus (STh)
addiction circuit: NT assoc (3)
- glutamate
- dopamine (DA)
- GABA
OXY: administration affect which summary
- OXY administration, systemically or into NAc/ STh sig reduced CPP reward/ relapse to meth-seeking behaviour
- local effect of oxy partially reverse by selective OTR antagonist when administered into NAc or STh
- effect of systemic oxy not reversed by systemic pretreatment w OTR antagonist
oxy admin reduced relapse to meth use through receptor mechanisms other than OTR (oxy receptors)
= possibly vasopression V1a receptors
vasopressin: periphery function (3)
- aka ADH
- diuresis (increases urine production) ADH release retains fluid in body (V2 receptors)
- regulates blood vol and ion (salt) conc.
- causes constriction of blood vessels to increase BP (V1 receptors)
vasopressin: in the brain- location, highest lvls, function
- also in SON, PVN neurons
- highest lvls of Vaso receptor binding in bed nucleus stria terminalis, central amygdala and nucleus accumbens
- effect on brain depends on receptor subtype activated
vasopressin: V1a activation
- prosocial effects
does oxy activate V1a receptors to reduce meth relapse?
vasopressin: V1b activation
- anxiety, fear, aggression
vasopressin receptor on oxy: summary
- effect of oxy to reduce meth relapse reversed by V1a receptor antagonist (admin sys or locally into NAc)
= suggests oxy admin is effective in reducing meth use through V1a receptor dependent mechanism
molecular neuropharmacology: FSCV aka
- fast scan cyclic voltammetry
molecular neuropharmacology: FSCV function
- electrochemical technique used to look in real time at conc. of NT released within circuit
- can measure electroactive NT (dopamine, NAd, serotonin)
molecular neuropharmacology: dopamine function
- important for motor, cognitive functions
- regulating reward processes
FSCV: features and mechanism
- carbon fibre microelectrode inserted into brain region of interest
- stimulator + cannula
- voltage applies to electrode, holds -ve potential and then to +ve potential (oxidation) then -ve (reduction)
- application of charge in triangular waveform repeated every 100ms
- change in current during oxi-redox process measured
FSCV: pros
- good spatial resolution
- good temporal resolution
Acetylcholine and addiction: type and location
- NT and neuromodulator
cell bodies located in:
- magnocellular basal forebrain system (medial septum, nucleus basalis of meynert, diagonal band of broca)
- brainstem system (pedunculopontine tegmental nucleus, laterodorsal tegmental nucleus)
Acetylcholine and addiction: list (2) receptors, locations and function (5)
- projections all around brain, also effect vol transmission
- muscarinic (metabotropic) and nicotinic (ionotropic) receptors
- involved in attention, memory, learning, mm movement and REM sleep
Acetylcholine and addiction: reward and addiction processes
- cholinergic input from pedunculopontine tegmental nucleus (PPTG) and laterodorsal tegmental nucleus (LDTG) stimulates dopamine release from VTA
- following exposure to drugs, cues assoc to drugs, increased acitivity in both PPTG and LDTG ACh neurons (increase firing of dopaminergic neurons in VTA)
cocaine administration summary:
- cocaine admin (experimenter given/ self-administered) increases dopamine firing in VTA and NAc pathway in animals previously exposed to cocaine
- cholinergic input from brainstem cholinergic sys stimulates dopamine firing in VTA
- in cocaine withdrawn animals, cholinergic input to VTA drives dopaminergic firing, not glutamate
- cholinergic activation of muscurinic receptors of VTA drive global reward processes, whilst activation of nicotinic receptors in VTA drive drug reward processes
overall summary: neuropharm
- neuropharm allows researchers to directly manipulate neural sys to see how they are activated/ inhibited and how this affects systems neurosci (behaviour, CVS etc.)
- help understanding how drugs abuse work, treat diff disorders and diseases
which (2) brain regions involved in memory of how good is drug use?
- hippocampus
- amygdala
OXY antagonist: reverses effect of OXY in what brain regions (2) and partially/completely?
- NAc: partially reversed
- STN: partially reversed
cocaine withdrawn animals: cholinergic input to VTA drives dopaminergic/glutamate/both firing?
- only dopaminergic firing
