EB - Psychoactive Drugs III Flashcards
What was amphetamine first synthesized from?
Ephedrine, a naturally occurring compound
What are the actions of amphetamine? (4)
- Appetite suppressant
- Euphoria
- Raised blood pressure
- Can cause psychosis
What are some clinical uses of amphetamine? (3)
- Weight control
- Narcolepsy
- Attention deficit disorder
Is methamphetamine used clinically?
No, methamphetamine is not used clinically.
It is a street drug, more addictive than cocaine
What is the mechanism of action of amphetamine (and methamphetamine)? (3)
- Prevents reuptake of dopamine into the presynaptic terminal.
- Reverse transport: Amphetamine is taken up into the nerve terminal instead of catecholamines, increasing catecholamine levels in the synaptic space.
- Results in higher dopamine levels in the synaptic space.
How do addictive and aversive drugs affect dopamine? (2)
- Addictive drugs like opiates, ethanol, nicotine, amphetamine, and cocaine increase the release of dopamine in the nucleus accumbens.
- Aversive drugs do not have this effect.
What are the pathways involved in addiction? (2)
- Evidence for common involvement of the limbic system.
- Dopamine signalling is especially involved, including the VTA projection to the nucleus accumbens.
How does dopamine affect the nucleus accumbens and cortex? (3)
- Dopamine has an inhibitory effect on neurons in the nucleus accumbens, which project to the cortex.
- These neurons are typically inhibitory, meaning they normally reduce activity in the cortex.
- Increased dopamine activity suppresses these inhibitory neurons, leading to disinhibition of the cortex (i.e., the cortex becomes more active).
What are the addiction stages?
Impulsive stage:
1. Substance use - pleasurable effects (e.g. euphoria)
2. Heavy use - craving the reward (positive reinforcement)
Compulsive stage:
3. Early dependence
4. Late dependence - withdrawal effects occur (negative reinforcement)
What are the long-term changes associated addiction in terms of D receptors? (2)
- D1 receptor activation (more available) causes an upregulation of adenylyl cyclase, converting ATP to cAMP.
- PKA translocates to the nucleus, phosphorylating CREB, leading to gene expression changes.
What is epigenetics?
Changes in gene expression that aren’t caused by underlying changes to the DNA sequence
Mediate effects of lifetime exposures
How are epigenetic changes related to addiction? (2)
- Epigenetic changes, like histone acetylation, alter chromatin structure and gene expression, contributing to addiction.
- Cocaine can induce histone acetylation in the nucleus accumbens
How does the loss of CBP affect cocaine-induced behaviors? (2)
- CBP (CREB-binding protein) is a histone acetyltransferase in the NAc.
- Loss of CBP in the NAc prevents cocaine-induced locomotion and conditioned place preference (CPP), suggesting CBP is necessary for cocaine’s effects on behavior.
What is the role of the Cre-LoxP system?
- The Cre-LoxP system allows gene manipulation at specific times.
- Cre recombinase interacts with LoxP sites to cut out DNA between them.
- This system is used to create knockouts or activate genes by removing stop codons.
What are the site-specific epigenetic changes after stimulant exposure? (5)
- Acute stimulant exposure rapidly induces genes like c-fos.
- Loss of CBP in NAc neurons decreases histone acetylation and alters c-fos expression in response to stimulants.
- After chronic stimulant exposure, these changes become desensitized.
- ΔFosB is induced by chronic stimulant use and binds to the c-fos gene.
- Chronic exposure leads to the loss of H3K9me2 at the Fosb gene, altering gene expression.
