Chronic Administration of Stimulants

Question 1

Tolerance

Answer 1

• shows in the drugs anorectic effects (reduction of appetite)
• tolerance occurs to this effect but only under certain conditions - provides insight into the nature of tolerance in general
• the development of tolerance to stimulant anorexia requires the contingent presentation of both the stimulant and the availability of food to food-deprived animals (all three conditions: drug, food availability and hungry rat - must be present which is why it’s known as ‘contingent tolerance procedure’

Question 2

Sensitization

Answer 2

• found that a dose of stimulant that initially produces only mild behavioural activation as its repeatedly given (a smaller dose starts to act like a bigger dose) and there is a shift to the left on the drug response curve
• potentially dangerous for frequent users that can have adverse effects
• stimulants are used to treat ADD but with the right doing regimes it is unlikely that sensitization would be seen if there is adherence to a prescribed regime
• animals tested with the usual drug cues demonstrated a “sensitized” behavioural response while animals tested in the nondrug context behaved similarly to control animals experiencing the drug for the first time
• placebo CR test demonstrated that animals expecting a stimulant but getting exhibited the hypothesized behavioural activation conditioned response

Question 3

Stimulant Psychosis

Answer 3

• psychotic, schizophrenic-like episodes
• maybe produced by a single acute administration of a high dose but its more often the case that stimulant psychosis may be produced in individuals who have been binging or who take daily doses over a longer period of time
• first seen in Japan after WWII
• characterized as: unpredicted swings between intense emotion and blunted effects, hallucinatory phenomena, paranoid ideation in a setting of clear consciousness, feeling small insects crawl on or under their skin (formication syndrome - “speed bugs” or “crank bugs”)
  Sigmund Freud described them as “white snakes”
• also produces obsessive-compulsive behaviour in humans (analogous to the stereotypies)
• psychotic episodes can be induced in people with no preexisting psychotic tendencies but it’s more readily occurs in diagnosed people - consistent with the hypothesis that psychosis is due to excess dopamine and the fact that stimulants increase dopaminergic activity (estimates up to 60% of regular users developing symptoms)

Question 4

Physical Dependance

Answer 4

• DSM V recognizes a stimulant withdrawal syndrome but it’s not required symptom for stimulant use disorder (less robust than to other drugs like alcohol, barbiturates, nicotine etc.)
• prominent difficulties when users try and stop are the presence of cravings - irresistible urge to take the drug to avoid withdrawal…
• if the user sees the drug stimuli they are more likely to experience cravings - these stimuli can be things like seeing where they use to shoot up, see the depiction of a line of coke etc. (changes in the brain have been shown on a PET scan)
• PET scans have shown that increased glucose metabolism, indicative of enhanced neuronal activity in various brain regions when drug stimuli are shown

Question 5

Neurotoxic Effects

Answer 5

• long term use of a drug may produce permanent damage to the brain with consequent mental, emotional and/or physical problems
• substantial evidence that long-term use of a drug (especially one that causes the release and block of the reuptake of both dopamine and serotonin) results in a decreased functioning and even neuron death
• the clearest evidence for this is methamphetamine
• there is also evidence of reduced functioning in methamphetamine and methcathinone abusers