introductory psychology: neuropharmacology iii
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Drugs & Behavior III: Amphetamines
Brian J. Piper, Ph.D.
Amphetamines
__
Amphetamine Methamphetamine
Amphetamines
Amphetamine Methamphetamine
___
3,4-methylenedioxymethamphetamine
Methyl: CH3; Methylene: CH2; Amine: organic compounds of Nitrogen,
History of Methamphetamine• 1893: Synthesized by Nagai Nagayoshi in Japan• 1940s- : Popular with military• 1960s- : used for short-term treatment of obesity, narcolepsy,
and, later, ADHD• 1983- : federal and states laws attempt to reduce use by
decreasing availability of ephedrine and pseudoephedrine• 2000s- : several aggressive advertising campaigns are aimed
at reducing demand
Montana Meth Project• Businessman Thomas
Siebel supported graphic advertising in 2005
• Goal was to reach each teenager 3+ times/week (TV, radio, print).
To View Ads: http://www.montanameth.org/View_Ads/index.php
True of False: “the MMP results in Montana have been more significant than
any other drug prevention program in history”?
Youth Risk Behavior Survey
• High School students were asked about lifetime methamphetamine use before and after the Montana Methamphetamine Project.
Anderson (2010) J Health Econ
True or False: “the MMP results in Montana have been more significant than any other
drug prevention program in history”?
Youth Risk Behavior Survey
• High School students were asked about lifetime methamphetamine use before and after the Montana Methamphetamine Project.
Anderson (2010) J Health Econ
Other Faces of Methamphetamine
Robert Downey, Jr.Andre Agassi
Stacy Ann Ferguson “Fergie” Ted Arthur Haggard
Other Faces of Methamphetamine
History of EcstasyEcstasy is 3,4-methylenedioxymethamphetamine (MDMA)
• 1912: Synthesized by German pharmaceutical company Merck by Anton Kollisch (1888-1916)
• 1950’s: U.S. Army conducted animals studies to determine the lethal dose.
• 1970’s: Mental health workers advocated using MDMA with psychotherapy. There are ongoing studies to use MDMA with talk therapy for anxiety related to post-traumatic stress disorder and among terminally ill cancer patients.
• 1985: Drug Enforcement Agency (DEA) classifies MDMA as Schedule I
• 1990’s- today: MDMA is popular recreational drug, especially among young-adults.
Short-term effects of Ecstasy
• Psychological– Empathy– Increased energy– Openness– Increased sensitivity to
sounds & touch
• Physiological– Increase in heart rate– Increase in blood pressure– Reduced appetite– Bruxism: grinding teeth– Trismus: jaw clenching
Example of tolerance• Rats received ecstasy
(MDMA) on 6 days. Arrows indicate times of administration.
• Panel A shows that MDMA altered core temperature on the 1st day.
• Panel B shows that the same dose had less effects on the 3th day.
• Panel C shows almost no effects by the 6th day.
Piper et al. (2005) Developmental Psychobiology, 47, 145-157.
Amphetamines
Amphetamine Methamphetamine
___
3,4-methylenedioxymethamphetamine
Methyl: CH3; Methylene: CH2; Amine: organic compounds of Nitrogen,
Chemistry
• Entactogen: touching within (Nichols)
Amphetamine
MDA (methylenedioxyamphetamine)
MDMA (methylenedioxymethamphetamine)
Ecstasy = MDMA?
Drug Levels in the Blood: Individual Differences Following Oral Administration of MDMA
Plasma MDMA for each marmoset thatreceived 1 mg/kg.
0 20 40 600
10
20
30
40
50
60
70
80
Eric
Autumn
Lexi
Zale
Time
MD
MA
(n
g/m
l)
Ng/ml
Age Influences How Your Body Responds to Drugs
MDMA -----> MDA
Meyer, Piper,& Vancolli (2010) Annals of the New York Academy of Sciences.
Brain Chemistry
• MDMA increases neurotransmitters (serotonin, norepinephrine, dopamine) & hormones (cortisol, prolactin)
Serotonin
• Serotonin is 5-hydroxytryptamine (5-HT)• The brain uses the amino acid tryptophan
(found in bananas, milk, yogurt) to make 5-HT.• 5-HT has been implicated in mood (anxiety,
depression & aggression), appetite, sexuality, and cognition.
See also: http://en.wikipedia.org/wiki/Serotonin
Raphe nuclei
• 5-HT cell bodies (somas) are found in the brainstem in the raphe nuclei.
• 5-HT axons descend into spinal cord and ascend to the hippocampus and cortex.
Serotonin Transporter (SERT)• SERT is a protein found at the synapse and
along the axon that removes 5-HT from the synaptic cleft.
• SERT (shown in pink) brings 5-HT from the synaptic cleft back into the axon.
• Serotonin reuptake inhibitors (e.g. Prozac or fluoxetine) prevent SERT from removing 5-HT.
• The density of SERT is used as a index of the number of 5-HT axons and is altered by MDMA.
Long-term effects of High Dose MDMA on 5-HT neurons (animal data)
• Weeks after MDMA treatment to animals, there is a reduction in 5-HT, 5-HT metabolites, and SERT which suggests a 5-HT axotomy (axons are cut).
• Months to years after MDMA in monkeys, some brain areas still show a reduction in SERT and 5-HT (hypoinnervation). However, other areas show an abnormal increase in SERT and 5-HT (hyperinnervation).
Serotonin fibers in the caudate nucleus of a control squirrel monkey (A), a monkey that received 5 mg/kg MDMA 2 weeks (B),
or 7 years (C) previously.
Hatzidimitriou, G. et al. J. Neurosci. 1999;19:5096-5107
What about brain function?
• Complex behaviors can be measured in non-human animals like:– Attention– Learning– Memory– “Emotion”
Object-Recognition Memory Task
Rats were exposed to two identicalobjects in a 3-min sample phase.
There was a retention delay (15 min),during which both objects were replaced:one replacement object was identical to theprevious two, while the other was a novelobject.
Memory of the familiar object isindicated by the animal spending moretime exploring the novel object during a3-min choice phase.
Figure from A. Ennaceur.
Adolescent MDMA decreases memory.
Saline MDMA
Sample (A) 25.6 (3.1) 23.5 (1.4)
Test (A) 11.8 (2.0) 14.9 (1.4)
Test (B) 24.7 (3.5) 20.0 (3.1)
B/(A+B) 0.68 (0.03) 0.56 (0.04)*
Piper & Meyer (2004) Pharm Biochem & Behav 79: 723-731
Adolescent MDMA reduces anxiety-like
behavior.
BEHAVIORSALINE-
TREATEDMDMA-
TREATEDP VALUE
Total arm entries 19.1 ± 3.0 27.4 ± 3.0 .074
Open-arm entries 3.1 ± 1.4 7.9 ± 1.8 .058
Open/Total (%) 12.8 ± 5.2 27.3 ± 5.3 .071
Open-arm duration (sec)
41.4 ± 18.7 108.9 ± 20.3 <.05
Closed-arm duration (sec)
507.4 ± 30.5 400.5 ± 30.3 <.05
Piper & Meyer (2004) Pharm Biochem & Behav 79: 723-731.
Piper & Meyer (2004) Pharm Biochem & Behav 79: 723-731.
Spatial Memory In Rodents• Rodent research has found that early developmental
Methamphetamine treatments cause persistent impairments in spatial memory.
Acevedo SF, de Esch IJ, Raber J (2007) Neuropsychopharmacology 32:665-672
MDMA Summary
• Short-Term Effects: – Empathy– hyperthermia, – ↑5-HT & Dopamine
• Long-Term Effects: ↓5-HT
Amphetamine Comparison
MDMA Methamphetamine
History One-century One-century
Acute Subjective Effects Empathy Euphoria
Neurotoxicity Serotonin Dopamine
Schedule I III
Addiction No Yes
Hallucinogens
Hallucinogens are psychedelic (mind-manifesting) drugs
that distort perceptions and evoke sensory images in the
absence of sensory input.
Ronald K
. Siegel
Hallucinogens
1. LSD: (lysergic acid diethylamide) powerful hallucinogenic drug that is also known as acid.
2. THC (delta-9-tetrahydrocannabinol): is the major active ingredient in marijuana (hemp plant) that triggers a variety of effects, including mild hallucinations.
http://static.how
stuffworks.com
Hemp Plant
DrugsSummary
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