Addiction Flashcards
Define addiction
when drug-seeking and use becomes compulsive despite negative consequences e.g. health risk – physical and mental, inability to sustain normal social interactions or job, dissolution of family, child neglect
What do all addictive drugs seem to do?
Increase levels of DA in the mesostriatal pathway
Describe the mesolimbic DA pathway
It projects from the VTA to nucleus accumbens in ventral striatum
Action of cocaine
Inhibits dopamine reuptake by DAT (the dopamine transporter) → more DA in the synaptic cleft
Action of amphetamine
Leakage of DA
Amphetamines enter the presynaptic terminal through the dopamine transporter, and initiate a reaction cascade within the plasma which promotes the reverse transported of dopamine out of their storage vesicles and then out of the neuron, into the synapse through the dopamine transporter
Action of nicotine
Stimulates VTA nAChRs
Binds to presynaptic nAChRs on both GABAergic and glutamatergic inputs to VTA neurons to increase their firing rate
Action of opioids
Inhibit GABA release
Act on μ opioid Rs →found on the pre-synaptic membrane of the GABAergic neurons in the VTA
Gi-coupled so levels of cAMP decrease → decreases activity of GABAergic neuron, increases firing of mesolimbic dopamine neuron, increased dopamine release
DISINHIBITION!
What is the hedonia hypothesis?
Original theory → that increased DA was responsible for the hedonic aspect of reward, which is why increased DA caused drug addiction
What is the prediction error hypothesis?
This states that DA signalling is not responsible for the hedonic reward sensation, but rather acts to predict reward based on cues; the actual reward value experienced then modulates dopaminergic signalling to keep predictions up to date
Describe mechanism of prediction error hypothesis
nucleus accumbens neurons → orbitofrontal cortex via the mediodorsal thalamic nucleus → this region is thought to encode the predicted value of different behaviours or items → feedback to the VTA to control firing rate
So, according to the PEH..
1. addiction drugs all increase DA release in the nucleus accumbens upon administration
2. this leads to strong positive reinforcement of their reward value every time they are used
3. according to the circuit described, this leads to dramatic overvaluation of drug in the OFC compared to behaviours or other items, which leads to compulsive drug-seeking behaviour, even in the face of negative consequences
How may plasticity of the system contribute to addiction?
- drug seeking may be triggered by drug-related cues
- these is an association between cues and the drug
- theory is that when someone uses addictive drugs, the dopamine release strengthens the neural connections association drug-related cues to drug-desires and seeking
Describe LSD
Psychotomimetic Behavioural effects: - Distorted perceptions - Hallucinations - Illogical thinking - Heightened sensory awareness - Not euphoric
Agonist at 5-HT2A R.
How it produces its effects is not known, but it could increase glutamate release in the cerebral cortex → excitation in this area
Describe MDMA
Psychotomimetic Behavioural effects: - Euphoria - Hallucinations - Feelings of intimacy, empathy - Bruxia, lockjaw - Hyperthermia
Acts primarily as a presynaptic releasing agent of serotonin, noradrenaline, and dopamine.
It also competes with monoamine reuptake transporters to inhibit monoamine reuptake
Describe cannabis
Psychotomimetic Behavioural effects: - feeling of well-being, disinhibition - sharpening of senses - amnesia, confusion - produces dependence?
THC = active ingredient Molecular effects: - CB1 and CB2 receptors - CB1 inhibits transmitter release - Endocannabinoids But THC indirectly causes DA release – addictive?
