EB NTs Psychoactive Drugs, and Addiction

Neurology

Biological and structural elements of the brain, physical disorders that impact the neurological system

Psychiatry

Focused on investigating mental and emotional illnesses

Neuropsychiatry

Intricate interaction between neurological and
psychiatric aspects

Telencephalon

Cerebral hemispheres

Mesencephalon

Midbrain

Diencephalon

Central core

Rhombencephalon

Brainstem

Ventricles

Four freely communicating, CSF filled cavities - enlargement seen in neuropsychiatric disorders

Thalamus

Relay station for sensory information

Thalamus circuit loop

Provides all parts of the neocortex with afferents, the thalamus receives input from the cortex. Also forms part of a circuit ‘loop’ with the striatum. Important in controlling input to the cortex

Basal ganglia

Extrapyramidal motor control, initiation and fine-tuning of movement

Limbic system

Regulates emotions and behaviour

Contents of the limbic system

Hippocampus
Fornix
Mammilary body
Thalamus
Cingulate gyrus

Amygdala

Ventral striatum

Amygdala

Emotional response to face recognition and involved in reward and addiction

Urbach-Wiethe disease

Calcium is deposited in the amygdala. Patients with bilateral lesions cannot discriminate emotion in facial expressions

Catecholamines

Adrenaline

Noradrenaline

Dopamine

Noradrenaline

Long axonal tracts, small diameter, highly branched

Originate from single nucleus (locus coeruleus)

Ascending NAdr-Medial forebrain bundle

Innervate limbic regions and areas controlling sensory input

Influence hormone secretion from pituitary

Key involvement in perception, attentional processes, mood, behaviour

Locus coeruleus (LC)

Part of reticular formation - role in arousal

Mesocortical pathway

Dopaminergic pathway affecting behaviour (VTA → Cortex)

Mesolimbic pathway

Dopaminergic pathway affecting behaviour (VTA → NAC)

Nigrostriatal pathway

Dopaminergic pathway affecting motor control (SN → Striatum)

Tuberoinfundibular pathway

Dopaminergic pathway affecting hormone secretion (Hypothalamus → Pituitary)

Serotonin (5-HT)

Monoamine neurotransmitter

Innervates limbic system

Level of neuronal activity increases the immediately prior to and during periods of activity in moving animals

Raphe nuclei

Site of serotonin synthesis. In the medulla - part of the reticular formation

Acetylcholine

Used in cholinergic pathways

Cholinergic pathway short projections

Interneurons, circuits within nucleus, local information processing

Cholinergic pathway long projections

From Nucleus Basalis of Myenert, axons innervate cerebral cortex, cognitive and behavioural function

Glutamate

Major excitatory transmitter with ubiquitous distribution

GABA

Major inhibitory transmitter with ubiquitous distribution

PET

Positron emission tomography

SPECT

Single photon emission tomography - doesn’t require on site cyclotron

Nuclear medicine imaging techniques

PET and SPECT

Mode of action for nuclear imaging

Unstable positron emission isotopes are created in a cyclotron and injected. They distribute according to the relative activity of the
brain regions. Can be used to estimate receptor levels

Psychotomimetic drugs

Cause profound changes in perception, mood and behaviour

Naturally occurring hallucinogens

Ayahuasca - active ingredient: DMT (+harmaline)

Peyote - active ingredient: mescaline

Magic mushrooms - active ingredient: psilobycin

LSD mechanism of action

Cross tolerance between LSD and mescaline, suggests that both psychotomimetics act at the same class of receptor site. Structures of LSD, mescaline, and 5-HT are similar

LSD interacts with 5-HT receptors, in the peripheral vasculature: 5-HT2 receptor antagonist, in the brain: 5-HT receptor agonist/partial agonist

Decreased levels of 5-HT metabolites in rat CSF after LSD administration

LSD altered perception

LSD decreases firing rate of raphe neurons (5-HT1A receptor). Raphe neurones send extensive projection to the forebrain. Mescaline does not affect raphe neuron firing

LSD and the locus coeruleus

LSD increases activity in locus coeruleus neurons. LSD increases activity of subsets of neurons in the cortex. 5-HT receptors in cortex
and thalamus modulate signal

LSD imaging

Increased visual cortex cerebral blood flow. Expanded primary visual cortex functional connectivity. Correlated strongly with ratings of visual hallucinations. Decreased connectivity between the parahippocampus and retrosplenial cortex. Correlated strongly with ratings of “ego-
dissolution” and “altered meaning,”