7 The addicted brain

• Sympathetic division

• Parasympathetic division

• Autonomic Nervous System

• Somatic Nervous System

• Somatic senses (Mechano receptors)

• Visceral (respiration, cardiac activity, sneizing)

• Special senses (hearing, smell, vision)

Sympathetic division of the Autonomic Nervous System (ANS)

Somatic Nervous System

enteric nervous system as part of the parasympatic division of the Autonomous Nervous System

Myelen- and Metencephalon

• medulla oblongata

• part of the Hindbrain

• Contains ascending and descending sensory and motor tracts connecting the cerebrum to the spinal cord

• Most spinal cord tracts cross over in the pyramids

• Contains nuclei that regulate breathing, blood pressure, vomiting

pons, cerebellum, reticular formation

• pons

  • Contains pneumotaxic centre which fine tunes breathing rate

  • Relays information between cerebellum and cerebrum

• cerebellum

  • Feedback center for execution of motor movements

  • Controls posture and balance

• reticular formation

  • Nuclei diffusely located through the brainstem

  • Regulates wakefulness and muscle tone, pain, sleep-wake circle

Thalamus

Cerebral Cortex

• the relationship between neurotransmitter systems and behaviour („neurochemistry of behaviour“) is the basis for psychopharmacology

• Psychopharmacology offers an explanatory approach of the therapeutic effectivness of several medications in clinical use

• GABA: gamma-Aminobutyric acid

• most abundant inhibitory neurotransmitter in the CNS

• GABA A (ionotrophic) and GABA B (metabolotrophic)

• Peripheral nervous system

  • Motor control

  • Acetylcholine functions very differently in the cardiac muscles. It stops the contraction of the muscles in the cardiac region

• Autonomic nervous system

  • Parasympathetic: pre- and post- parasympathetic neurons

  • sympathetic neurons: pre- sympathetic neurons, also post in the sweat glands

• Central nervous system

  • Arousal

  • Reward

  • Plasticity

  • REM sleep is promoted

• Serotonin pathways in the brainstem area “the Raphe nuclei”

• frontal cortex: regulates cognition and memory.

• hippocampus: regulates memory

• in the other limbic areas: regulate mood

Physiological and pathophysiological roles include:

• In periphery: peristalsis, vomiting, platelet aggregation and haemostasis, inflammatory mediator, sensitization of nociceptors and microvascular control.

• In CNS, control of appetite, sleep, mood, hallucinations, stereotyped behaviour, pain perception and vomiting

6

• Mesolimbic Pathway:

  • Associated with pleasure, reward and goal directed behavior

• Mesocortical Pathway:

  • Associated with motivational and emotional responses

• Nigrostriatal Pathway:

  • Involved in coordination of movement (part of basal ganglia motor loop)

• Tuberoinfundibular Pathway:

  • Regulates secretion of prolactin by the pituitary gland and is involved in maternal behavior

• Area postrema:

  • Controls vomiting

• PNS

  • Most neuromuscular and neuroglandular junctions of sympathetic divisions of ANS

  • Control of body temperature

  • Regulation of pituitary gland secretion

  • Contracts blood vessels

  • Increasing blood flow

• CNS

  • - Location in cerebral cortex, hypothalamus, brain stem,cerebellum, spinal cord

  • Involved in attention and consciousness

• modulatory Neurotransmitter

• Modulation of wakefulness, motor activity, food intake, sexual behaviour

• Effects on H1-receptors (allergic reaction) and H2-receptors (gastric acid secretion

• Food, water, sex and nurturing are natural rewards

• They allow organisms to feel pleasure

• They reinforce the behaviour of repetition

• These are required for survival

• The brain has pathways and circuits for reward

• Drugs of abuse hijack physiological reward mechanis

any event that increases the probability of a response with a positive hedonic component

In the 1950s, Olds and Milner implanted electrodes in various regions of the rat brain to systematically determine which neuroanatomic areas could reinforce self-stimulation

They identified the mesolimbic system as the brain circuit responsible for feeling pleasure

• tune attributes of rewarding stimuli by encoding the value of a reward

• creating incentive salience for reward

• enhancing associative learning of the reward context

• determining the predictability of a reward

• Rewards activate the neurons

• Expectation of rewards activates the neurons

• Absence of expected rewards inhibits the neurons

• Unexpected rewards activate the neurons even more!

Reward circuits

• A stimulus that causes a response to be maintained and increased.

• Positive reinforcement: increases behavioral response to get a positive reward (food, sex, etc.).

• Negative reinforcement: increases behavioral response to end the anhedonic situation.

• In this way, rewards and reinforcements in the environment, powerfully shape an individual’s behavior

… begin to respond to the conditioned stimulus (i.e., the sight of the drug, the refrigerator door, the gambling casino).

• VTA dopamine neurons are controlling reward

• Drugs directly and powerfully activate these neurons with no connection to purposeful behavior

• This leads to a profound corruption of the brain’s reward mechanisms: drugs gradually, progressively, and insidiously replace natural rewards as the major shaper of behavior

Drug addiction can be defined as a chronically relapsing disorder, characterised by compulsion to seek and take the drug, loss of control in limiting intake, and emergence of a negative emotional state (e.g., dysphoria, anxiety, irritability) when access to the drug is prevented.

Addiction is continued use of a substance despite harms that outweigh the benefits, with a lack of control over substance use.

• Reduced responses to natural rewards.

• Sensitized responses to drugs of abuse and associated cues

• Impaired cortical control over more primitive reward pathways

• Drug abuse results in a higher production of receptor proteins + structural proteins (adaptation to the drug)

• This leads to changes in behavior consistent with addicted states

• Addiction is therefore a form of drug induced neural plasticity

Methamphetamine increases dendritic spine densitiy

Substances which are both rewarding and positively reinforcing