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What is the mesolimbic pathway?
• dopaminergic neurons in the ventral tegmental area project to the nucleus accumbens, prefrontal cortex, olfactory tubercle, amygdala
Dopamin ____ is in turn _____ by nicotinic acetylcholine receptors. What is this important to?
• modulation • modulated • indirect path
What symptom is Parkinson’s can nicotine reduce?
dyskinesia
What extinguishes nicotine self-administration?
• 6-OH dopamine lesions of dopaminergic terminals in the nucleus accumbens
What receptors are responsible for nicotinic addiction?
• alpha4 nAChRs
Which pathways/areas contribute to nicotinic addiction?
• mesolimbic dopaminergic pathway • anterior cingulate cortex and hippocampus • lateral septum ventral and amygdala • lateral hypothalamic area and paraventricular and arcuate nuclei • hypothalamic-pit-aden axis and hippocampus and frontal cortex
What symptom of nicotinic addiction does the mesolimbic dopaminergic pathway cause?
• pleasure and relieve craving
What symptom of nicotinic addiction does the anterior cingulate cortex and hippocamppus cause?
• improvement in cognitive function, attention, learning and memory
What symptom of nicotinic addiction does the lateral septum ventral and amygdala cause?
• reduction in stress and anxiety
What symptom of nicotinic addiction does the lateral hypothalamic area, paraventricular and arcuate nuclei cause?
• decrease appetite
What symptom of nicotinic addiction does the hyothalamic-pit-aden axis, hippocampus, and frontal cortex cause?
• relieve depression
What other factor is also involved in nicotinic addication?
• social pressures
What does chronic nicotine intake result in in terms of modulation?
• upregulates nicotine binding - more nAChR receptors in many brain areas
In what areas do we see a significant increase in alpha4 nAChR expression?
• VTA (TH+) DA (NS) • VTA (GAD+) GABA • SNC (TH+) DA (NS) • SNR (GAD+) GABA • Nucleus accumbens (NS) • proportionality GABA increases more
We see a shift in the intensity of GABAergic neurons with nicotine use, what does this indicate?
• chronic nicotine increases alpa4 receptors in GABAergic and not dopaminergic neurons
What is increased by chronic nicotine?
• increases firing rates of GABAergic midbrain neurons - increases basal firing and response to nicotine
What is decreased by chronic nicotine?
• decreases firing rates of dopaminergic midbrain neurons - decreases basal firing and response to nicotine
What does the circuit based mechanism of tolerance of reward tell us?
• GABAergic to dopaminergic • saline and first use: greater firing in dopaminergic for anticipation and reward • chronic nicotine: more firing in GABAergic for anticipation (craving) and reward (decreased reward)
What does chronic nicotine exposure cause in the ventral tegmentum?
• upregulates nACh receptors on GABAergic neurons - no effect on nAChR levels in dopaminergic neurons
What does the effect of chronic nicotine exposure on the ventral tegmentum cause?
• lower basal dopamine release - suppression of dopamine release when exposed to acute nicotine
Why might you see dopamine release increase during exposure to acute nicotine?
• increases only to reach or slightly exceed the levels that normally exist as basal levels in naive animals
Why do both nicotine and cocaine cause addictions?
• they use the same pathway • craving and tolerance result • different places in pathway that drug has effect
Where does nicotine have it’s effect in DA neurons and GABA interneurons?
• GABA and dopamine neurons - at glutamate inputs to dopaminergic neurons of VTA and nucleus accumbens?
Where does cocaine have it’s effect?
• at synapse of dopaminergic neurons