Test 4: Drugs of Abuse pt 1 Flashcards
The economic burden of addiction is estimated at more than ___________ annually in the United States.
The economic burden of addiction is estimated at more than $400 billion annually in the United States.
What is addiction?
-Psychological dependence on a drug
-Compulsive drug use despite negative consequences
-Triggered by cravings and contextual cues
-Not the same thing as dependence (Dependence occurs with chronic exposure - only a small amount of users become addicted)
-Relapse is common even after successful withdrawal.
What is the brain pathway associated with addiction?
The Mesolimbic pathway (also referred to as the reward pathway)
-A Dopaminergic pathway
-Connects the Ventral Tegmental Area (midbrain) to the Nucleus Accumbens.
-Most significant neural pathway in the brain for addiction.
What is the Ventral Tegmental Area (VTA)?
Located in the midbrain
-Dopamine producing neurons
-Releases large quantities of dopamine to the nucleus accumbens and prefrontal cortex.
Systemic administration of drugs of abuse causes the release of dopamine.
What are the receptors associated with the 3 classes of addictive drugs?
1) GPCR
2) Ionotropic Receptors
3) Dopamine Transporter
What addictive drugs are included in Class 1 (GPCRs)?
-Opioids
-Cannabinoids
-Gamma-Hydroxbutyric Acid
-Lysergic Acid Diethylamide-25
-Mescaline (peyote)
-Psilocybin (mushrooms)
What is the MOA of the Class 1 drugs (GPCRs)?
Increased Dopamine due to inhibition of GABA.
Targets the GABA neurons of the VTA.
Inhibit neurons via:
-Post-synaptic hyperpolarization – K+ (harder to depolarize - receptor will not fire)
-Pre-synaptic regulation of transmitter release – Ca++ (can’t release NTs from the presynaptic membrane without Caclium)
Inhibit the inhibitors, resulting in excitation of the system.
What is the MOA of opioids?
-Target MORs in the VTA, located exclusively on GABA neurons
-Presynaptic inhibition of voltage-gated Ca channels
-Postsynaptic activation of K+ channels, causing K efflux and hyperpolarization
Together, the pre and post synaptic mechanisms reduce NT release and suppress activity, taking away the inhibition by the GABA neurons.
How do Cannabinoids work on a cellular level?
-Δ9-tetrahydrocannabinol (THC) and other cannabinoids mainly act through presynaptic inhibition. (CB1R, cannabinoid receptors)
-THC stimulates CB1 receptor to decrease release of GABA (indirectly increasing Dopamine)
How does Gamma-hydroxybutyric acid (GHB aka roofies) act on a cellular level?
-Gamma-hydroxybutyric acid (GHB) targets GABAB receptors, which are located on both cell types.
-However, GABA neurons are more sensitive to GHB than are DA neurons, leading to disinhibition at concentrations typically obtained with recreational use.
-Therapeutic use with Narcolepsy.
What drugs fall under Class 2 (Ionotropic receptors)?
Nicotine
Benzodiazepines
Barbiturates
Alcohol
Ketamine
Phencyclidine
Nitrates, ketones, hydrocarbons (inhalants)
What is the MOA of the drugs in Class 2 (Ionotropic)?
Direct release of Dopamine from neuron.
Ionotropic: Ligand gated ion channels
-Opened by something that will trigger the receptor.
-Weakly sensitive to RMP
-Combines the effects of Dopamine and GABA neurons
-Increases the release of Dopamine.
What drugs are in Class 3 (Dopamine Transporter)?
Cocaine
Amphetamines
What is the MOA of the drugs in Class 3 (Dopamine transporter)?
Increased Dopamine due to blocking of transporters.
-Block dopamine reuptake, allowing for more circulating dopamine in the system.
-Stimulate non-vesicular dopamine release (release of dopamine not stored as a vesicle)
-Also blocks cytoplasmic transporter and the transporter that puts it into a vesicle.
-Causes an accumulation of extracellular dopamine in the target structures = excitation.
-Also effects the transporters of other monoamines (NE and 5HT)
What are the beneficial effects of Cannabinoids? (Why used in medical therapies)
Increased appetite
Attenuation of nausea
Decreased intraocular pressure
Relief of chronic pain
