Test 2: NT Flashcards
Monoamine Hypothesis of Depression
Depression results from reduced activity of brain monoamines. BUT NE and 5-HT agonists change levels immediately, but do not have therapeutic effects for about 2 weeks.
SO…Receptor Super Sensitivity Hypothesis:
Receptors were sensitive to begin with. Bc this, brain downregulated amount of 5-HT. Taking meds adds NTs to the body and brain can’t “turn it down” so receptors are reset.
How do we know depression results from reduced activity of brain monoamines?
- Reserpine depletes monoamines –> depression
- Suicidal depression is related to a low level of 5-HIAA
- Antidepressant meds increase either NE or 5-HT
- Usually via blockade of monoamine reuptake
- Tryptophan deletion procedure:
- Reduces brain 5-HT levels
- Reinstates depression in former depressed patients
What are some drug treatments for depression?
- Tricyclics (block reuptake of NE and 5-HT)
- MAOI
- SSRI (Serotonin)
- SNRI (Norepinepherine)
- NDRI (NE and DA)
Are drugs effective compared to talk therapy?
About the same. Combined-best.
Drug therapies-only slightly more effective than placebo
Treatment for Bipolar Affective Disorder
Anticonvulsants-used to reduce extreme activity in cortex during manic phase
Lithium carbonate
-70-80% of patients show positive response
-Most effective in treating manic phase, then dep does not follow
-Does not suppress normal emotions or intellectual processes
-Many side effects, must have regular testing to avoid overdose
-Do not know how it works
What is glutamate (glutamic acid)? How does it leave the synaptic cleft?
- excitatory NT
- Glial cells take it up (no reuptake)
What are the four receptor types glutamate interacts with?
- NMDA (controls CA2+ channel and a sodium channel)
- AMPA (sodium channel)
- Kainate (sodium)
- Metabotropic glutamate receptor (around 7 different types-some are autoreceptors)
GABA
- Induces IPSPs (inhibitory)
- synthesized from glutamic acid by means of GAD (glutamic acid decaboxylase) enzyme
What receptors does GABA act on?
GABAA
-Ionotropic receptor (controls a chloride channel)
-Contains 5 different binding sites: GABA site, Benzodiazepine site, Barbiturates, Steroid binding site, Picrotoxin binding site
GABAB
Metabotropic receptor (controls a K+ channel)
See diagram of uptake in glial cell for glutamate and GABA
See diagram of uptake in glial cell for glutamate and GABA
Indirect GABA agonists
- Benzodiazepines-facilitates GABA effect-tranquilizing effect
- Alcohol (may bind to benzo site)
- Barbiturates-sodium pentothal-causes GABA to remain bound longer therefore keeping channels open longer
- Overall effect of calming, but too much may lead to coma, unconsciousness, even death.
Peptides
- Consist of 2 or more amino acids (linked by peptide bonds)
- Are synthesized in the soma and transported to axon terminal in vesicles
- Are released from all parts of the terminal button ad after release are enzymatically degraded (no reuptake)
- Can be co-released with other NTs (can serve as a neuromodulator)
Opioid Peptides: Opioids vs Opiates
- Opioids-endogenous
- Opiates-exogenous. Overall reduction of pain
Opioid Receptors
- Mu-Endorphins. Located in brain stem. Most related to addiciton. 1-euphoria, analygesia 2. Respiratory depression
- Delta
- Kappa
- Sigma
Drug Addiction Involves:
- Persistent drug-taking
- Stimulation of brain positive SR mechanisms
- Unsuccessful efforts to stop drug-taking
- Drug interference with social/occupational functions
Drug Dependence: Physical vs Psychological
Physical dependence-adaptive state in which:
-Increased experience with drug leads to reduced drug action
-Cessation of drug-taking leads to intense physiological disturbances (withdrawal. Typically the opposite of the normal drug action)
Psychological dependence is a condition in which:
-Taking a drug produces a pleasurable state
-A person is motivated to take the drug in order to maintain a pleasurable state in or avoid discomfort
Know about + and - SR in drug taking
Know about + and - SR in drug taking
Know about classical conditioning and overdose
Know about classical conditioning and overdose
Know about drug craving and classical conditioning.
NS can acquire incentive salience (CS). Exposure to CS results in drug craving
Which receptors may mediate drug craving?
D3
Other effects of opioids
analygesia, hypothermia, sedation, and SR
Opioid receptors and addiction
- Mu receptors-SR and analygesic
- Kappa-aversive action of opiates . Dynorphin-stimulates kappa-aversive. Found within PAG, ventral tegmentum and nuc. accumbens
Role of Nuc. Accum. DA in Opiate SR
Opiate administration into the ventral tegmental area or the nuc. accum
Opiate SR does not solely involve the mesolimbic DA system
-6-OHDA lesions of the nuc. accum. reduced self-admin of cocaine, but not of heroin
-Lesions of the nuc accum blocked the formation of a conditioned place preference for amphetamine, but not for morphine
Presynaptic model for opiate addiction
- Opioids-presynaptic inhibition of CA2+ channels to prevent release of Sub P
- Excessive opiates trigger autoreceptors to shutdown terminals
- Withdrawal occurs when opiates are removed and body must compensate with pain without opioids until normal function is returned
Orexin/hypocretin
Involved in activation/arousal/wakefulness. Located in lateral hypothalamus.
Endogenous ligands for cannabinoid receptors (2)
- Anandamide
- 2-arachidonyl glycerol
Nitric oxide
Soluble gas-can diffuse widely to exert actions on distant cells
Adenosine
-Nucleoside
-Breakdown of ATP (energy molecule) when cells
need fuel/energy
-Usually inhibitory – coupled to G protein, activates
K+ channels, generates an inhibitory postsynaptic
potential
-Involved in the control of sleep – possibly inhibit
cholinergic basal forebrain neurons which may be
responsible for wakefulness/cortical desynchronized
EEG evident during wakefulness
-Caffeine – blocks adenosine receptors, so you get
excitatory effects
