I got a few books in this area, but best book in my opinion is

Drugs & Behaviour: An Introduction to Behavioral Pharmacology by William McKim (click image).





Biopsychologists usually use pharmacology (drugs) to study the behavioural effect of neurotransmitters


Drugs have 2 effects on synaptic transmission:

Agonists: drugs that facilitate the effects of a neurotransmitter

Antagonists: drugs that inhibit the effects of a neurotransmitter


Neurotransmitters: complex chemicals made from proteins by enzymes

Precursors: basic NT building blocks coming from amino acids from our diet


Neurotransmitter steps (see also Essential Biopsychology):

  1. synthesis of neurotransmitter (NT)
  2. storage in vesicles
  3. breakdown by enzymes of any NT
  4. Exocytosis
  5. Inhibitory feedback via autoreceptors
  6. Activation of postsynaptic receptors
  7. Deactivation (enzymes, reuptake)



Neurotransmitter Drug Function Effect Mechanism Agonist Antagonist

Table from Drugs & Behavior: An Introduction to Behavioral Pharmacology by William McKim


1. Small Neurotransmitters

Amino acid

  • e.g. GABA



               – e.g. norepinephrine (NE): eating control, attention & arousal; stress response. Converted from DA by enzyme dopamine Beta-hydroxylase

               – e.g. dopamine (DA): pleasure; addictive drugs; schiz = high DA; alx = low. Is from precursor amino acid tyrosine and converted to L-DOPA by enzyme DOPA decarboxylase


Acetylcholine (ACH) cholinergic neurons vital to learning and memory; alzheimer’s & dementias have fall in cortical ACh


Serotonin (5-HT) serotonin is made from precursor amino acid tryptophan (e.g.bananas). Enzymes add/subtract molecular components in a step by step fashion.


Unconventional neurotransmitters


  1. Large Neurotransmitters




Arvid Carlson, Dopamine & Parkinson’s Disease (1957)

  1. Discovered DA is an active NT in its own right (not just precursor of NE)
  2. Discovered role of DA in movement
  • reducing DA in animals disrupted motor control
  • restoring DA levels by giving DA precursor >> restored control
  • let to treatment of Parkinson’s using L-DOPA
  • Parkinson’s is a result of depleted DA
  • L-DOPA is a precursor of DA and therefore a DA agonist


Henri Laborit (surgeon), Dopamine & Antipsychotics (1952)

  • noticed that chlorpromazine led to “indifference and relaxation” in patients
  • drug had great effect on schizophrenics
  • schiz: disordered thought, emotions & perceptions
  • chlorpromazine decreases DA transmission in mesolimbic system
  • chlorpromazine is a postsynaptic receptor blocker of D2 receptor


Cocaine: blocks DA reuptake via DA reuptake transporters

Amphetamine: both blocks reuptake & triggers release of DA into the synapse


Ellinwood (1968) – amphetamine

Users report: increased energy, distortion of cognition, improvement in self-image

ordinary events become more significant and universe makes sense

drug seems connected with exploration process

objects stimulate curiosity & search for new categories & significance

users engage in repeated assembly & disassembly of objects

OC: large doses for days >> symptoms of schiz: hallucinations & confused thought

paranoia. This would be the extreme behavioural effect of DA


Volkow et al (1997) – cocaine

Gave cocaine to addicts asking them to rate the ‘high’

  • intensity of the highs was connected with how much the cocaine bound to DA transporters
  • no high experienced unless drug bound to 50% of DA transporters


Tobler et al (2005) – nucleus accumbens (n.acc)

Mesotelencephalic DA system: axons from neurons in ventral tegmental area project into the nucleus accumbens. This pathway is connected in natural rewards and addictive drugs. System has a reinforcing effect (e.g. food, sex = good)

  • dopaminergic neurons in this pathway reflected experience & expectation of reward, especially difference between expectation and actual reward



– opiate drugs have both excitatory & inhibitory effects

– opiates mimic the effects of opioid neuromodulators

– they stimulate opioid  receptors in various parts of the brain

– inhibitory effects: reduced sensitivity to pain (neurons in midbrain), hypothermia

(hypothalamus), sedation (medulla)

– overdose kills by stopping neuronal circuits in medulla that control breathing, heart rate & blood pressure

– some opioid receptors are located on DA secreting neurons so heroin produces feelings of euphoria and pleasure



Serotonin secreting neurons inhibit mechanism responsible dreaming

LSD suppresses this activity >> dream mechanisms activate >> hallucinations

Phil & LeMarquand (1998) – low brain 5-HT >> aggression

suggest a serotonin behavioural inhibition system – restrains

aggression & impulsive behaviour


Adrenaline & Noradrenaline

Holmes (1994) – cause increase in blood cholesterol levels when person under stress

related to release of free fatty acids >> increased HR & BP





see my essay plan on serotonin: here



– there are at least 14 different serotonin receptors in different areas of the brain & body

– serotonin affects subsets of various neuronal circuits in different ways

– role in sleep, dreaming, mood, sex, anxiety, feeding and pain



– Inhibitory: tends to calm things down

– depression linked to too little 5-HT

– we have a natural bias to negativity and lowering 5-HT >> more negativity

– linked to appetite

– sleep disturbance



Phil & LeMarquand (1998) – aggression

– low brain 5-HT >> aggression

– suggest a serotonin behavioural inhibition system: restrains aggression & impulsive behaviour


Klaassen et al (1999) – cognitive & mood

– depletion of serotonin precursor tryptophan >> cognitive impairment, esp LT memory

– caused lower serotonin turnover in brain

– can lower mood only where there’s family history of depression: so indiv diffs


Blundell & Halford (1998) – appetite

– serotonin has a role in appetite suppression

– serotonergic drugs have been shown to reduce hunger, eating and bodyweight



Psychoactive drug: a chemical acting primarily on the CNS, altering brain function and changes e.g. consciousness, mood, behaviour, perception


Iproniazid (1957) – Monoamine Oxidase Inhibitor

– the first antidepressant: was intended to treat TB – patients seemed unconcerned about TB

– was tested on psychiatric patients and seemed to work for clinical depression

– monoamine agonist against MAO enzyme, increasing levels of monoamines (e.g. 5-HT)

– takes 1-3 weeks to take effect [OC: does that say anything about effectiveness etc?]

– cheese effect side effect where cheese and wine raise blood pressure


Imipramine (1958) – tricyclic antidepressant

– the first tricyclic antidepressant: was intended to treat schizophrenia

– no effect against schiz but helped depressed

– blocks reuptake of monoamines which inc. NE and serotonin, increasing their levels


SSRIs – selective serotonin reuptake inhibitors e.g. Prozac

– block reuptake of serotonin only

– claimed to work against fear of failure, self-esteem, anhedonia


Birmes et al (2003) – serotonin syndrome

High doses of SSRIs can cause visual hallucinations, confusion, fever


Stimmel (2006) – sexual dysfunction

Patients treated with SSRIs can have problems with orgasm, erection and desire


Kirsch et al (2008)

– antidepressants didn’t perform much better than placebos for mild depression

– OC: so drawing conclusions about NT effects from drugs problematic


Moncrieff & Cohen (2009) study (see below) – concludes we don’t know



– 2003 indication may cause suicide but not proven >> decreased use >> increased suicide

– OC: so evidence that serotonin has role in mood/ depression & backs up medical model





– a serotonin-like psychedelic drug with a structure similar to serotonin

– binds to serotonin 5-HT2 receptors causing hallucinations and disturbances in thinking

– serotonin inhibits mechanisms that cause dreaming

– LSD suppresses activity of serotonin secreting neurons >> hallucinations


– why doesn’t serotonin produce extreme psychosis? e.g. SSRIs

– there are cases, however, of serotonin syndrome



– ecstasy affects the serotonin pathway

– neurons in the pathway send axons to neocortex & limbic system (e.g. amygdala & hippo)

– when serotonin binds to receptor usually leads to less firing

– ecstasy (a) binds to reuptake transporters and (b) causes transporters to go into reverse



ARTICLE: Moncrieff & Cohen (2009) – “How do psychiatric drugs work”

– question assumption that drugs work on the neurochemical causes of a disorder

– rather drugs simply cause a drug induced state

Disease/medical centered model: biological causes; psychiatric drugs correct an abnormal brain state

Drug centered model: drugs put a person in a different mental & physical state

– traditional view that drugs act on the cause and other effects are side effects

– Moncrieff argues drugs are psychoactive, producing general not specific therapeutic fx

– psychoactive effects of drugs (motor slowing, sedation etc) could be effective in lots of disorders (e.g. sleep disturbance or arousal)

– suggest disorder specific drugs are no more effective than other psychoactive drugs e.g. opium

– drugs which aren’t antidepressants (e.g. benzodiazepines) have similar effects to antidepressants (special status of antideps not justified)



– no strong evidence that DA abnormality itself causes psychosis instead of DA related activity e.g. arousal or stress

– some effective antipsychotic drugs (e.g. clozapine) have weak action on DA receptors

– monoamine hypothesis the same: no evidence of NA/5-HT deficiency in depressed people

– antidepressants are claimed to work by correcting lack of these (NA/5-HT)



– drugs shouldn’t be said to target specific diseases because of lack of evidence

– they should be said to produce certain states and patients can decide whether good/bad

– it’s difference bet. “this drug targets bio cause of depression” and “this drug produces an altered state”

– researchers must detail effects of drugs on thought, emotion and body





– role in movement, memory, problem solving, emotion, attention, reinforcement

– involved in brain mechanisms of reward & pleasure: sex, eating, drugs etc



– 50s discovery that DA antagonists (e.g. chlorpromazine) have a calming effect



– schizophrenia = high DA

– parkinson’s = low DA

– DA theory of schiz questioned

– DA associated with attention


Dopamine Hypothesis & Schizophrenia

– found that antischizophrenic drugs (e.g. chlorpromazine) had calming effect

– antischiz drugs also cause tremor at rest and reduction in voluntary movement

– hypothesis that DA was cause of schiz symptoms: hallucinations, incoherent speech etc

– heavy cocaine (reuptake blocker) users have symptoms indistinguishable from schiz

– OC: so excessive DA activity causes extreme sensory awareness?


– DA hypothesis questioned e.g. takes weeks to have an effect


Parkinson’s Disease

– caused by degeneration in nigrostriatal pathway >> less DA transmission

– difficulty initiating movement so DA has role in movement

– the DA precursor L-dopa is used to treat parkinson’s


Dominguez & Hull (2005) – sex

– DA facilitates male sexual behavior in all studied species, inc. rodents & humans

– DA antagonists (in medial preoptic area) impair copulation, genital reflexes, and sexual motivation



– cause DA to leak into the synapse, increase the amount of DA produced after AP & block reuptake

Hedblom & Grinspoon (1975) – self reports: exhilaration, energy, motivation, clear mind

Weiss (1969) – attention task: amphetamine >> consistent accuracy vs controls

– OC: studies like these confirm DA role in attention



DeWit et al (1997)

– drugs that block D1 & D2 receptors don’t block amphetamine euphoria

– other drugs copying cocaine’s action at DA synapses don’t cause euphoria

– so other brain systems and perhaps NTs involved in the effects



– reuptake blocker

– effects similar to amphetamines


Reward, Addiction, Reinforcement

– the most powerful addictive drugs are powerful CNS DA releasers

– ICSS and place preference studies implicated DA in reward and addiction

– lesions in the dopaminergic pathways disrupt ICSS

– DA agonists increase ICSS; antagonists decrease it

– Volkow et al (2004): user-reported cocaine highs related to how much it bound to DA reuptake transporters

– other studies: increase in DA levels with expectation, presentation or experience of addictive drug or natural rewards


focus on DA systems but not just DA: e.g. Koob (2006) – highlights the role of GABA and other systems


Söderqvist (2012) – memory

– review: numerous studies indicate that DA is important in working memory function

– pharmacological interventions (e.g. methylphenidate) acting on the DA system improve WM


– some debate about the types of tasks improved (e.g. spatial or other) and receptor subtypes involved






– From Cannabis plant and has around 400 compounds: most important is THC

– can remain vital for up to 30 days

– 50% of UK university respondents report having used it (Ashton 2001)



– effects varied

– low dose can stimulate appetite, reduce anxiety, well-being, relaxation, vivid perception

– high dose can produce panic attacks, paranoia, create psychedelic experiences

– high dose attention, short-term memory impaired

– psychomotor similar to alcohol: slower reaction time, coordination impaired

– mood changes from euphoria to dreaminess to anxiety



Rey et al (2002) – higher use associated with higher levels of depression

– cannabis interacts with the the brain’s cannabinoid (CB) receptors

– CBs have a range of important roles in neurodevelopment and cannabis use can cause disruption

– cannabis also indirectly >> DA release; DA dysfunction widely implicated in schiz

– elevates risk when combined with psychosocial factors & genetic vulnerability



– THC affects the endocannabinoid system & receptors widely found in the brain

– cannabinoids from the postsynaptic neuron attach to presynaptic cannabinoid receptors

– this affects the behaviour at the presynaptic neuron on AP (like feedback loop?)

– THC attaches to cannabinoid receptors and disrupts their ‘fine tuning’ function



Cannabis use (especially before age 15) has been linked to the onset of schiz

How does it work?

  1. cannabis interacts with brain’s cannabinoid (CB) receptors
  2. CBs have important roles in neurodevelopment
  3. cannabis use causes disruption at this critical age
  4. cannabis indirectly >> DA release: DA linked to schiz
  5. all this increases risk combined with neg psychosocial & genetic disp factors


Zammit et al (2002)

– followed group of Swedish males for 25 years

– controlled for confounding variables

– concluded cannabis increases risk of schiz

– THC increases release of DA: there is an established link between DA & schiz


– correlation doesn’t prove causation: are young pre-schiz attracted to cannabis?

– OC: also DA hypothesis challenged


Arendt et al (2005)

– study of 535 patients treated for psychotic symptoms caused by cannabis

– 44% showed schiz type symptoms

– 47% got a diagnosis of cannabis induced schiz 1 year after going for psychosis treatment


– there was a significant gap before schiz type symptoms

– didn’t control for any other type of substance abuse during the period of the study

– could be users have other pre-existing problems & use other substances


Smit (2003) – review of studies

– did a review of longitudinal studies linking cannabis to psychosis or schiz

– evaluated a number of competing hypotheses e.g. not cannabis but another factor is cause

– conclude: cannabis roughly doubles risk of schiz

– risk gets larger the more cannabis is used

– risk is larger in vulnerable people (e.g. genetic predisposition)