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Cocaine and the NAcc
inhibits re-uptake of DA from VTA axon terminals and increases DA levels directly at synapses in NAcc
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Amphetamine/methamphetamine and the NAcc
causes DA release from VTA axonal projections and increases DA levels directly at synapses in NAcc
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Opioids and the NAcc
Opioids can increase NAcc DA levels through disinhibition of VTA neurons by inhibiting GABAergic projections to VTA
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Nicotine and the NAcc
can increase DA levels in the NAcc by activating VTA neurons; stimulates ACh release to VTA from lateral hypothalamus
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Three different glutamate receptors...
- AMPA, NMDA, Kainate.
- All ionotropic.
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AMPA
Glutamate receptor; allows NA+ in.
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Kainate
Glutamate receptor; allows NA+ in.
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NMDA
- Glutamate receptor; allows Ca2+ in.
- Depolarization expells Mg2+ from channel.
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Why is NMDA receptor called the "coincidence detector"?
Because it opens following another excitatory event.
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What is long term potentiation?
Synaptic connects are strengthened for at least an hour. Requires activation of NMDA receptors for induction and AMPA receptors for its expression.
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Neurons from what areas of the brain converge on the NAcc? (4)
Prefrontal cortex, ventral pallidum, ventral tegmental area, and the basolateral amygdala.
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How can a glutamate antagonist alter activity of MSNs on the NAcc?
If a glutamate antagonist blocks glutamate release from prefrontal cortex, hippocampus, and amygdala axonal projections, glutamate receptors in the NAcc are not activated and the release of GABA from the NAcc is inhibited.
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What is a common effect of drugs of abuse on the NAcc?
To decrease stimulation of GABA MSNs in the NAcc.
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What are the effects of D1 DA receptors? (2)
- -stimulate adenylate cyclase and increase cAMP
- -stimulation elicits self-grooming behavior
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What are the effects of post-synaptic D2 DA receptors? (3)
- -inhibits adenylate cyclase and decreases cAMP
- -Enhances K+ channel opening
- -Activation increase locomotor activity and sniffing
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What are the effects of presynaptic D2 DA receptors? (2)
- -decreases DA release by reducing Ca2+ entry (autoreceptor)
- -Increases removal of DA from synapse (regulates function of DA transporter)
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What is the effect on receptor levels with use of a long-term agonist?
Receptor down-regulation
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What is the effect on receptor levels with use of a long-term antagonist?
Receptor up-regulation
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Describe the nigrostriatal DA pathway.
Cell bodies in the substania nigra; axon terminals in the dorsal striatum. Effects motor function.
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Describe the mesolimbic DA pathway.
Cell bodies in the VTA; axon terminals in the NCaa and olfactory tubercule. Important in reinforcement.
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Describe the mesocortical DA pathway.
Cell bodies in the VTA; terminals in the cerebral cortex. Important in decision making.
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What is the endogenous NT for opioid receptor agonists?
Endorphine
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What is the endogenous NT for cannabinoid receptor agonists?
Anandamide
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What is the endogenous NT for NMDA receptor agonists?
Glutamate
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Describe Olds and Milner's experiment with ICSS.
Olds and Milner trained rats to hit a lever by stimulating specific brain sites when the behavior was performed.
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List several behaviors that result in dopamine release in the nucleus accumbens.
ICSS, feeding, drinking, sexual behavior, self-adminstration of drug reinforcers, gambling.
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What is the major class of neurons located in the NAcc?
GABAergic medium spiny neurons
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List the 3 types of classical NTs.
Amino acids, monoamines, and acetylcholine.
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What NTs are monoamines?
Dopamine, serotonin, norepinephrine.
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What NTs are amino acids?
Glutamate, GABA
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Name the 3 types of non-classical NTs.
Neuropeptides, lipids, and gases.
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What NTs are neuropeptides?
endorphines, corticotropic releasing factors
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What NTs are lipids?
anandamides (ex. cannabinoid receptors)
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What are ways in which neurotransmission is terminated?
Diffusion, uptake, or enzymatic degredation.
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What are the subdivisions of the hindbrain?
Myelencephalon and Metencephalon.
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What is the subdivision of the midbrain?
Mesencephalon
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What are the sub divisions of the forebrain?
Telecephalon and diencephalon
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What are the sub divisions of the metencephalon?
Cerebellum and pons
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What are the subdivions of the telencephalon?
Neocortex, basal ganglia, and limbic system.
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What are the sub divisions of the diencephalon?
Thalamus and hypothalamus
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The myelcephalon is the location of what?
The area postrema = vomit center; contains opioid receptors.
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What are the two important sub divisions of the pons?
Raphe nuclei and locus coeruleus
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What NT is the locus coeruleus mainly responsible for?
It primarily synthesizes norepinephrine. Activation results in arousal and attention.
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The raphe nucleus primarily synthesizes what NT?
Serotonin. Generally inhibitory in the CNS
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What is the function of the cerebellum?
It is the sensorimotor center. Controls balance and movement.
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What is a primary function of the Periaqueductal gray (PAG) area?
Important in pain regulation. Dense concentration of opioid receptors.
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Why is the substantia nigra important?
It projects serotonergic axons to the striatum. It is responsible for the initiation of movement.
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What is the function of the VTA?
- It project dopaminergic neurons to olfactory tubercle, nucleus accumbens, amygdala, prefrontal cortex, etc.
- Important in drug addiction.
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What is a function of the basal ganglia?
Contains the dorsal striatum. With substantia nigra is motor center. Important for habitual memory.
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What is an important function of the Limbic System?
- Includes limbic cortex, amygdala, hippocampus and nucleus accumbens.
- Integrates emotional responses and regulates motivated behavior and learning
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Why is the nucleus accumbens important?
Important for the reinforcing effects of almsot all drugs of abuse.
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