Neurophysiology of Drug Addiction (Karius) Flashcards
in producing pleasure, the VTA sends increased amounts of this NT to the Nac..
Increased dopamine
the core of the reward/pleasure system consists of these 2 areas..
Ventral segmental area (VTA) Nucleus accumbens (NA)
the VTA receives excitatory input from these 3 areas…
pre-frontal cortex
Lateral hypothalamus
laterodorsal tegmental nucleus
the prefrontal cortex, laterodorsal tegmental nucleus, and lateral hypothalamus provide excitatory input to the VTA via these NTs…
prefrontal cortex: EAA
Lateral hypothalamus: Orexin
laterodorsal tegmental n.: Ach
the VTA provides a dopamnergic input to the NAc via the __
median forebrain bundle
in addition to the dopaminergic VTA input, the NAc also receives EAA from these areas…
Prefrontal cortex
Amygdala
hippocampus
output from the NAc is to the pre-frontal cortex via this NT…
GABA
NAc also sends a GABA-ergic input back to the VTA
opioid inputs to the VTA inhibit a subset of GABA-ergic interneurons. This increases the release of __ in the NAc
Dopamine
___-receives inputs and releases dopamine in the NAc to lead to feeling of pleasure
VTA
___-part of striatum. D1- activate direct; D3- inhibit indirect pathways. When active, GABA is released to produce pleasure
NAc
___-receives input allowing pleasure from NAc
Pre-frontal cortex
Outline the Core system pathway of producing Pleasure …
Prefrontal cortex, Laterodorsal tegmental nucleus release increased EAAs & Lateral hypothalamic nucleus releases increased Orexin onto VTA —> VTA releases increased amounts of Dopamine onto NAc —> NAc decreases GABA release onto Pre-frontal cortex –> Pleasure
Outline the pathway for Preventing/absence of pleasure..
Prefrontal cortex, amygdala, and Hippocampus release increased amounts of EAA onto NAc –> NAc releases increased amount of GABA onto prefrontal cortex –> Absence of pleasure
The pleasure/reward system is what type of feedback system?
positive feedback
which D receptors are inhibitory?
D2 and D3
Major action of opioids in the reward/pleasure system?
Inhibit GABA interneuron in VTA –> VTA releases more dopamine in NAc –> intense feeling of pleasure (euphoria)
To produce pleasure, what happens to the following?
VTA=__
NAc=__
GABA in the prefrontal cortex=__
Activate the VTA
Inhibit the NAc
Less GABA in prefrontal cortex
To inhibit pleasure, what happens to the following?
NAc=___
GABA in the prefrontal cortex=___
Activate the NAc
More GABA in prefrontal cortex
___=changes in the anatomy and physiology of synapses associated with learning. Some changes are permanent, others more transient
Synaptic plasticity
___=Increase in response to same stimulus. Changes in both pre- and post-synaptic neurons which include increased NT release and increased post-synaptic responses d/t changes in the receptors to which NT binds
Long-term potentiation
What drugs work by activation of GPCRs?
Opiates=agonist at opioid receptors
Cannabis=CB-1 receptor, leads to DA release
What drugs work by alteration of ion channels?
Nicotine=agonist at NAChRs, influx of Na
Ethanol/PCP=Anatagonist at NMDA receptors (weak)
What drugs work by interference with re-uptake mechanisms?
Cocaine=Inhibition of re-uptake of DA –> increase in DA availability at synapse
Amphetamines=reversal of DA reuptake transporters
Ethanol activates the opioid inputs, particularly to the __
VTA
PCP and ethanol disrupt EAA inputs to the __
NAc
What other agents increase activity of VTA dopaminergic neurons?
cocaine
amphetamines
cannabis
Nicotine activates NAChR on __ neurons and induces the release of dopamine
VTA
the vast majority of addictive drugs lead to an increase in the dopamine release within the __ which leads to euphoria or an exaggerated reward response to even mild stimuli
NAc
activation of __ within the locus ceruleus and periaqueductal grey are associated with the physical dependence on drugs. Mechanism is unclear
CREB
the increase in __ release from the NAc turns the input from the VTA off, reducing the effect of the drugs. This is part of the process of desensitization that occurs with drug addiction
Dynorphin
Within the NAc, ___ has been shown to lead to production of proteins (e.g. BDNF) that are responsible for remodeling of the dendrites that occurs. Has a longer lasting effect than CREB and mostly associated with anatomic changes in synapses (more synapses, more dendritic spines)
Delta fosB
