Neurobiology of Drug Addiction, Opiates & Heroin Flashcards
List the two major mechanisms by which drugs affect the brain.
- Increase DA release in nucleus accumbens (NAc) and pre-frontal cortext (PFC).
- Interact with NE and/or 5HT neurons in brainstem.
These pathways are highly adaptive, leading to tolerance and dependence. Repeated or sustained exposure to many drugs involved in substance use disorders leads to synaptic adaptations in one or more of the above pathways; these adaptations resemble learning in many ways. Long-term potentiation (LTP) or long term depression (LTD), are known to occur at DA and other synapses in the NAc, VTA and other reward structures. Many signaling pathways appear to be involved.
List the DA-associated neural pathways implicated in addiction.
- VTA –> NAc –> DA release; reward, behavior reinforcement.
- VTA –> PFC –> DA release; cognitive aspects of reward & learning.
- SN –> CPu –> DA release; habit learning, compulsive behaviors.
SN = substantia nigra
CPu = caudate nucleus and putamen
List the NE-associated neural pathway implicated in addiction.
LC –> forebrain, cerebellum –> NE release; arousal, alerting, focused attention.
LC = locus ceruleus
List the 5HT-associated neural pathway implicated in addiction.
RN –> forebrain, cerebellum –> 5HT release; mood, visual functions.
RN = raphe nuclei
Heroin - Initial Use
- Often aversive; nausea and emesis common.
- Some pleasurable effects (brief, few minutes) – mild euphoria to the “rush” (~ sexual orgasm) that occurs when levels of heroin or morphine increase in the brain rapidly.
- Euphoria/sedation/dissociation (3-4 hours).
Heroin - Continued Use
Desire to re-experience the ‘rush’ and subsequent mood elevation with mild sedation. Important driver of IV heroin use. Once physical dependence is established, avoidance of withdrawal symptoms drives continued drug use.
Heroin - Consequences of Use
Repeated use of opiate drugs by the oral, systemic, or i.v. routes may have only negligible consequences on general health, if…
- sterile precautions for IV drug administration are taken
- opiate is taken regularly to maintain a significant level of μ-opioid receptor occupation (usually 2+ doses per day)
BUT self-administered illicit drugs are seldom sterile and drug availability is unreliable.
Heroin - Risks of Chronic Use
- overdose - most heroin is “cut” with inactive contaminants, effective dose will vary from batch to batch
- infections - dirty syringes, shared needles, contaminats - skin ulcers (at point of injection), embolism, and infection (most commonly HIV, bacterial endocarditis, and hepatitis)
- psychological consequences - increasing concern with obtaining and using drug, reducing interest in other activities; disturbed eating habits (malnutrition)
- social consequences - theft, pimping, prostitution
Heroin - Chronic Use
Tolerance is marked!
- Reduced effects of heroin.
- Cross-tolerance of all drugs acting thru mu-opiate receptors.
Physical dependence develops at the same rate as tolerance.
- Withdrawal syndrome develops within 6-12 hr.
- Triggered by opiate antagonists (naloxone, naltrexone). Give small amount to diagnosis opiate dependent state.
- Suppressed by giving more heroin/opiate (cross tolerance).
- Withdrawal is rapid but severe for short-acting opiates (heroin); withdrawal is slower and milder with long-acting methadone.
Heroin - Stages of Withdrawal
(Time after last dose) Symptoms.
- (6-12 hr) Lacrimation, rhinorrhea, yawning, sweating, anxiety.
- (12-14 hr) Restless sleep.
- (16-96 hr) Mydriasis, anorexia, gooseflesh, restlessness, irritability, tremor, weakness, depression, nausea, vomiting, intestinal spasms (stomach cramps), diarrhea, muscle and back pains, muscle spasms, CNS stimulation (ejaculation in men, orgasm in women); weight loss, acid-base balance changes, dehydration, and ketosis.
- Psycological - severe drug craving, lasting months to years.
Max severity at 48-72 hours after last dose; physical withdrawal symptoms abate within 7- l0 days. Effects of withdrawal are seldom life-threatening except in previously sick individuals.
Opiate Withdrawal in Newborns
- Symptoms - irritability, excessive high pitched crying, tremors, violent sucking on fists, hyperactive reflexes, increased bowel activity, vomiting, and fever.
- Treatment - administration of an opiate to reduce symptoms on a progressively decreasing schedule.
Note - Symptoms may be more severe in babies of methadone-maintained mothers than of heroin-addicted mothers.
Opiates - Mechanism of Tolerance v. Dependence
Tolerance – neurons become less sensitive to the drug; NO change in metabolism, distribution, or excretion.
Dependence - neural pathways develop enhanced activity to compensate for the depression in function induced by opiates; abnormal response in drug withdrawal bc drug leaves body faster than the pathways can adapt.
