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Feb 25, 2021

  

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PSY 340 Brain and Behavior

Class 09: Substance Abuse and Addiction

   

 
 

Celebrity
                Overdose Deaths

Leading Causes
              of Death in US 1959-2018


Surging Rates of Heroin & Prescribed Opioid Deaths in the US

Drug
            Overdoses by Sex 1999-2017
Drug
            deaths by age

Opioid
            Deaths

Drug Deaths in US (map) 2003 vs. 2017



Who is dying? "Deaths of Despair" (overdose, suicide & alcohol-related deaths)
among White non-Hispanic non-college graduates
  Changes in Mortality 1999-2015
Deaths
                of Despair


I. Drug Mechanisms

Types of Drug Effects

Drug
            Effects on Dopamine SynapsesOther Qualities of Drugs


II. Similarities and Differences among Addictive Substances

Self-stimulation in ratJames Olds & Peter Milner (1954) found areas in rat's brain which leads to continual self-stimulation. Pressing the lever in the experimental situation (see diagram on left) appears to have been very reinforcing for the rats. All of these areas associated with reinforcement eventually were seen to increase the release of dopamine in the nucleus accumbens (see diagram). 

Most drugs of abuse are likely to increase the release of dopamine and norepinephrine with effects on the n. accumbens. Some have labeled this area "the pleasure area" and dopamine as "the pleasure chemical." But, this label is very misleading.

Research in the last several decades points to dopamine as involved in more than the reinforcement Olds & Milner found in 1954. As the National Institute of Drug Abuse (NIDA, 2020) reported "The neurotransmitter dopamine helps people remember the pleasurable effects of drugs and reinforces the desire to seek them out again, making it centrally involved in addiction. Relatedly, dopamine neurons are also involved in “prediction errors,” responding when the value of a reward is more or less than expected...[R]esearch suggests that dopamine neurons are carrying much more information than previously thought…” 
 
Cravings. Recent studies suggest that dopamine and the nucleus accumbens play an important role in attention-getting or arousal. Addiction seems to have a quality of demanding attention (increasing your craving or wanting something = salience) and this may be the link (rather than via the "pleasure" effects of chemicals)

Reinforcement (= reward) involves both

Note that individuals with addiction show an overwhelming urge to get the drug even after the pleasure has stopped.

Research

Tolerance and Withdrawal.

Over time as addiction develops, the enjoyable effects of the drug tends to decrease. This is called tolerance. The addicted individual must use more of the drug to achieve the same level of reward. A great deal of the phenomenon of tolerance involves learning, i.e., conditioned and strengthening associations between the setting and mechanisms of drug ingestion and the body's response to the drug. Indeed, repeated exposure to typical drug use settings without actual drug use will weaken the association.

However, whenever an addict is exposed to settings in which he/she has typically used the drug, there can be a very strong reaction even if no drug is ingested. This reaction is called withdrawal. Symptoms of withdrawal include anxiety, sweating, vomiting, and diarrhea for opioids and tiredness, shaking, sweating, nausea, convulsions, and hallucinations for chronic alcohol abuse.  

Is all drug use in chronic drug users an attempt to avoid withdrawal symptoms?


Some Drugs of Abuse (not in book) 

   1. Stimulant drugs (e.g., amphetamines, cocaine, etc.)

a. Amphetamine increases dopamine (DA) release from presynaptic terminals and also reverses the direction of the dopamine transporter (reuptake gate) which makes more DA available.

b. Cocaine ("coke") blocks the reuptake of DA, NE, and serotonin at the synapse. The behavioral effects of cocaine are believed to be mediated primarily by dopamine and secondarily by serotonin.

c. The effects of amphetamine and cocaine are both short-lived, because of the depletion of dopamine stores and tolerance.

d. Methylphenidate (Ritalin®): Stimulant currently prescribed for Attention Deficit Disorder (ADD); works like cocaine by blocking reuptake of dopamine at presynaptic terminals. The effects of methylphenidate are much longer lasting and less intense as compared to cocaine.

--> the use of Ritalin® when used as prescribed does not lead to the use of other drugs in later life.

e. MDMA (methylenedioxymethamphetamine or "Ecstasy") at low doses is a stimulant which increases the levels of dopamine. At higher doses it releases serotonin and may have hallucinogenic effects.

[Don't
        Smoke]   2. Nicotine

Stimulates the nicotinic receptor (a type of acetylcholine [ACh] receptor) both in the central nervous system and neuromuscular junction of skeletal muscles. CNS nicotinic receptors tend to lie on neurons which release DA in the nucleus accumbens.
 
Nicotinic receptor stimulation leads to increased responsiveness and activity levels in novel settings

    3. Opiates [or opioids] (Narcotic: Derived from (or similar to those derived from) the opium poppy)

[Poppy
            Cultivation & Heroin]
Common opiates include
Opiates affect different receptor types in the brain.
They will also decrease (inhibit) other opiate receptors & cause a range of effects such as analgesia (pain relief), decreased respiration, lowered motility of the GI system (anti-diarrhea), and physical dependence.
   4. Marijuana

5. Alcohol and Alcoholism

[Effects
          of ETOH on body]

A. Alcoholism or alcohol dependence: A common type of substance abuse that produces significant harm to people's lives, and those people often find themselves continuing to drink in excess even after deciding to quit or reduce their drinking.

B. Alcohol (ethanol, ETOH): Inhibits Na+ ion flow across the neuron membrane; decreases serotonin activity, facilitates transmission at the GABAA receptor, blocks glutamate receptors, and increases dopamine activity. Thus, alcohol is mostly an INHIBITORY substance.

C. There have been multiple attempts to classify subtypes of alcoholism. One important effort was undertaken by the researcher Robert Cloninger on the basis of adoption studies among Scandinavian alcoholics. The two subtypes in his classification scheme (Oreland et al, 2017) are:

Type I Alcoholism: This type of alcoholism is less dependent on genetic factors and has a late onset, that is, it develops gradually over years (> 25 years old). It tends to affect men and women equally, and is generally less severe. It is often the result of years of leading a stressful life and using alcohol to cope with the stress.

Type II Alcoholism: This type of alcoholism has a strong genetic basis and a rapid and early onset (< 25 years old), affects men primarily, is more severe, is associated with the use or abuse of other substances, and reflects others social problems, e.g., a family history of alcoholism, depression, and antisocial or criminal behavior (fighting & arrests)

D. Predispositions for Alcoholism & Substance Abuse

i. Alcoholism: Tends to be more likely among those who, as children, were described as impulsive, risk-taking, easily bored, sensation-seeking, & outgoing.

Associated with genes causing

ii. Among sons of alcoholics, alcoholism is associated with

iii. Genetic influences on drug abuse

iv. Environmental Influences



This page was first posted January 18, 2005.

REFERENCES

Active/Lethal Dose Ratio and Dependence Potential of Psychoactive Drugs. Data source: Gable, R. S. (2006). Acute toxicity of drugs versus regulatory status. In J. M. Fish (Ed.),Drugs and Society: U.S. Public Policy, pp.149-162, Lanham, MD: Rowman & Littlefield Publishers. Image retrieved from http://en.wikipedia.org/wiki/File:Drug_danger_and_dependence.svg

Case, A., & Deaton, A. (2017, Spring). Mortality and morbidity in the 21st century (Brookings Papers on Economic Activity). Washington, DC: Brookings Institution. Retrieved from https://www.brookings.edu/wp-content/uploads/2017/08/casetextsp17bpea.pdf

Kimball, J. W. (2005). Synapse. Kimball's biology pages [Online]. Retrieved February 1, 2005 from the Web site: http://users.rcn.com/jkimball.ma.ultranet/BiologyPages/S/Synapses.html

NIDA (2020, March 27). Dopamine neurons signal rich information about unexpected events. https://www.drugabuse.gov/news-events/science-highlight/dopamine-neurons-signal-rich-information-about-unexpected-events

Oreland, L., Lagravinese, G., et al (2017). Personality as an intermediate phenotype for genetic dissection of alcohol use disorder. Journal of Neural Transmission. doi:10.1007/s00702-016-1672-9

Torregrossa, M. M., & Taylor, J. R. (2016). Neuroscience of learning and memory for addiction medicine: From habit formation to memory reconsolidation. Progress in Brain Research, 223. doi: 10.1016/bs.pbr.2015.07.006