Substance use disorder

What is the addiction cycle, and why is it considered intertwined?

The addiction cycle consists of compulsion, substance use, and pharmacological effects. It is intertwined because each stage influences the next, creating a feedback loop that reinforces addiction.

How do opioids act in the VTA to increase dopamine release?

Opioids stimulate Mu opioid receptors (MOPRs) on GABAergic neurons in the VTA, inhibiting GABA release. This disinhibits dopamine neurons, leading to increased dopamine release in the nucleus accumbens (NAcc).

What happens to noradrenaline during opioid withdrawal?

During opioid withdrawal, there is a massive increase in noradrenaline release in the locus coeruleus, leading to symptoms like irritability, anxiety, and increased heart rate.

What is the role of Mu opioid receptors (MOPRs) in the nucleus accumbens?

MOPRs in the medium spiny neurons of the NAcc reduce GABA release onto GABAergic interneurons, decreasing inhibition and increasing dopamine signaling.

What is the main cause of death in opioid overdose?

The main cause of death in opioid overdose is respiratory depression, caused by the suppression of the brainstem's respiratory centers.

How does methadone help in opioid addiction treatment?

Methadone is a long-acting synthetic opioid that acts as an agonist at MOPRs. It reduces acute withdrawal symptoms, tolerance, and dependence, and its dose is tapered over time.

What is the role of naltrexone in opioid addiction treatment?

Naltrexone is an MOPR antagonist that blocks the effects of opioids, reducing cravings. It can also be used in emergency situations to reverse respiratory depression but may precipitate withdrawal.

How do stimulants like cocaine and amphetamines increase dopamine release?

Stimulants increase dopamine release in the brain, leading to prolonged action and availability of dopamine at the synapse in the nucleus accumbens (NAcc), reinforcing addictive behavior.

What are the effects of cannabinoids on the brain?

Cannabinoids act on CB1 receptors, which can lead to overexcitation of the prefrontal cortex or amygdala, contributing to anxiety, paranoia, or cognitive impairment.

What are the two main subtypes of nicotine receptors, and what are their roles?

The two main subtypes are:

• α4β2: Located in the reward pathway, responsible for addictive qualities.

• α7: Associated with improved cognition and concentration.

How does nicotine cause rapid dopamine release but short-lived effects?

Nicotine receptors (nAChRs) desensitize quickly, causing a rapid increase in dopamine release but for a short period of time. After desensitization, they become inactive for a period.

How does bupropion help in smoking cessation?

Bupropion inhibits dopamine and noradrenaline reuptake and antagonizes nAChRs. It has a smaller but more prolonged effect compared to nicotine, making it less pleasurable and helping individuals quit smoking.

What is the mechanism of action of varenicline in nicotine addiction treatment?

Varenicline is a partial agonist of α4β2 nAChRs. It increases dopaminergic tone in relevant brain areas, reducing cravings and withdrawal symptoms, and helps maintain abstinence.

What are common triggers for smoking, and why are they significant?

Common triggers include:

• drinking coffee

• taking breaks at work

• talking on the phone

• drinking alcohol

• driving

• spending time with friends.

These situations are significant because they create cues that can lead to cravings and relapse.

What happens to nicotine receptors (nAChRs) after prolonged exposure to nicotine?

Nicotine receptors desensitize quickly after exposure to nicotine, leading to a rapid increase in dopamine release but for a short period of time. After desensitization, the receptors become inactive for a period, reducing their responsiveness.