Drugs of abuse Flashcards
Mesolimbic pathway role in addiction and drug abuse
Involved in producing reward and pleasure to encourage goal driven behaviour.
Drugs of abuse increase dopamine release from VTA into the nucleus accumbens, e.g., opioids, nicotine, amphetamines, cocaine, ethanol, weed, etc…
Opioids increase DA release by inhibiting the GABA interneurons that act as a feedback loop on DA neurones. Less inhibition of DA release.
Ethanol and nicotine increase DA neurone firing rate
Reward experiments
Rats will selfadminister rewarding drugs, and DA can be seen to increase in the VTA from micro electrode recordings.
Rats with microdialysis recording of the EC fluid in conscious rats measure the NT release, seeing that DA increase in the following drug administration
Drosophila larvae were put on a sugar containing plate (rewarding) with a specific odour. On another plate, without the sugar, the drosophila were still drawn to the odour, identifying a reward and reinforcement pathway. Produced a conditioned response.
Dulling of normal stimuli
with chronic use, they alter the gene expression, which reduces the reward associated with normal stimuli - effectively dull the world, unless drugs used.
down-regulation of chronic use of agonists, up-regulation of chronic use of antagonists
Tolerance of cocaine
In a binding assay, cocaine was found to bind significantly less (must higher ki value) in individuals with a history of cocaine use. Shows tolerance at DAT.
Cannabis
Activates Gi CB1 and CB2.
stimulates appetite through actions on the feeding centres in the hypothalamus, and possible mechanism in the GIT.
Study found CB1 agonist Anandamide increased DA levels in the nucleus accumbens.
SERT vs DAT addiction potential
Drugs that have lower ki (more affinity) for SERT than DAT generally are seen to be less addictive, e.g., MDMA and LSD. May be used to predict addictive potential.
