Psychomotor stimulants:

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• Psychomotor stimulants
• Chapter 11
• Cocaine
• Amphetamines
• Sensorimotor activation, alertness, arousal,
  excitement

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11.15 Amphetamine and related psychostimulants

• Family of synthetic psychostimulants
• All related structurally to DA

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11.16 Khat for sale in an Ethiopian marketplace

• Contains naturally occurring plant compound,
  similar in structure to amphetamine
• Ephedra similar herbal remedy

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• Development of amphetamine
• Ephedra now banned appetite suppressant
• In 1920s, ephedrine used for asthma
• Led to search for synthetic substitute
  amphetamine inhaler
• Later marketed for narcolepsy
• Pseudoephedrine still used as bronchodilator

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• Amphetamine pharmacology
• Indirect DA agonist
• High dose MAOI
• Also NA release, central and peripheral
• Elimination half life 7-30 hours
• But some take repeated iv injections

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11.17 Mechanisms of amphetamine-stimulated DA
release

• AMPH taken up by DAT
• Inside terminal provokes DA release
• Plus DAT functions in reverse to further release
  DA

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Amphetamine psychosis (Griffith et al., 1972)

• Participants (n 7) users but no prior history
  of psychosis
• Given 10 mg dextroamphetamine every hour for up
  to 5 days
• All became psychotic within 2-5 days
• Delusions mostly auditory, also included
  poisoning by experimenters and electric dynamo
  thought control

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The Ministry of Truths Drug Experiences Page
I started taking speed (dextroamphetamine)
orally to help me shift a bit of weight that I'd
put on in the last year. On the Saturday
afternoon when the psychosis began I just felt a
bit odd. My brain didn't seem to be connected to
my mouth and I had to really concentrate to be
able to form words. I felt detached and
distracted. Dark Shadows have been in the house
for the last few days. Tonight they are all over
the place in every corner and even under the
chairs. They were driving me mad looking for them
last night. The Dark Shadows have been inside
Wayne (my husband) for much longer but up until
very recently they only ever made brief outings.
I wonder how they got in there in the first
place. They use his eyes more often than he does.

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• Adverse effects
• Psychotic reactions
• Delusional beliefs
• Methamphetamine violence
• Methamphetamine flashbacks
• Neurotoxicity
• DA reduced DAT density
• 5-HT particularly Ecstasy

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11.18 PET images of reduced striatal DAT binding
associated with psychostimulant abuse

• Abstinent drug users
• DAT shown with radiolabelled cocaine
• Reduced in drug users and PD
• McCann et al. (1998)

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11.19 Reduced serotonergic fiber density in the
neocortex of squirrel monkeys treated with MDMA
Frontal
Parietal

• Fibres stained to show white
• 5 mg/kg MDMA twice daily for 4 days
• Killed 2 weeks or 7 years later

Visual
saline
MDMA
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• MDMA Ecstasy
• Developed in 1914
• In 1970s used therapeutically
• Termed entactogen
• Indirect 5-HT agonist
• 5-HT neurotoxin

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• Conditioning and addiction
• Primary withdrawal
• Followed by relapse in drug-taking environment
• Reports that lavatory smell elicits craving
• Addicts shown video of heroin preparation and
  administration report anxiety and craving

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• Principles of association
• During learning
• CS UCS gtUCR
• (bell) (food) (salivation)
• After learning
• CS gt CR
• (bell) (salivation)

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• Principles of association
• During learning
• Stimulus A Stimulus B gt Thought of B
• (word ball) (sight ball) (mental image ball)
• After learning
• Stimulus A gt Thought of B
• (word ball) (mental image ball)

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• Compensatory CRs
• Result in an aversive withdrawal reaction
  (counterbalancing action overshoots)
• If blood sugar is repeatedly increased by glucose
  injection, placebo injection results in decreased
  blood sugar level
• If blood sugar level is repeatedly decreased by
  insulin injection, placebo injection results in
  hyperglycaemia

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• Tolerance and sensitization
• Administration schedule
• Behavioural response measured
• Time elapsed since last dose
• Short ? tolerance
• Long ? sensitization

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• Agonistic CRs
• Stewart et al. (1984) have evidence for
  conditioned incentive effects
• A little of what you want makes you want more,
  like peanuts

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• Incentive motivation
• Reinforcers are incentives that elicit responding
• Reinforcer priming pre-trial reinforcer can
  increase run speed in rats (Terry, 1983)
• Salted peanuts effect (Hebb, 1949)

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Research here in Nottingham
Associative learning increased under psychomotor
stimulants

• Amphetamines increase CS salience in variety of
  procedures
• Latent inhibition
• Overshadowing
• Trace conditioning
• Contextual conditioning

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Amphetamine CER noise CS tests (Norman
Cassaday, 2003)
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Amphetamine CER light background tests (Norman
Cassaday, 2003)
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Methylphenidate CER noise CS tests (Horsley
Cassaday, 2003)
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Methylphenidate CER light background tests
(Horsley Cassaday, 2003)
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Treatment implications

• Pharmacological
• DA antagonists?
• Behavioural
• Avoid triggers for relapse
• Counterconditioning even better
• Psychosocial
• Counselling and support
• CBT and cue exposure

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Box 11.2 Psychostimulants and ADHD

• Adolescent rats
• Studied in active phase of cycle
• At lower dose, paradoxical reduction in activity
• Kuczenski Segal (2002)