Drugs + tourettes and ocd

Question 1

Describe the principal mechanisms of action as well as use and abuse of drugs targeting the dopamine transporter (DAT).

Answer 1

Coke: blocks DAT –> more dopamine in synaptic cleft
- Amphetamine: reverse dopamine reuptake (vMAT, DAT) –> more dopamine in synaptic cleft

Question 2

Describe the principal symptoms of Tourette’s Syndrome and of Obsessive-Compulsive Disorder.

Answer 2

Tourette:
- multiple motor tics
- at least one vocal tic that persist for > 1 year
- daily/almost daily

Question 3

Describe how negative reinforcement is involved in the habituation of tics, compulsions and obsessions..

Answer 3

Negative reinforcement: increased likelihood for absence will be repeated

Tics: if not supressed –> premonitary urges are released (itch, pressure, lump in throat ect.) –> relief
- negative: changing a behavior to avoid a negative experience

• habituation to premonitary urges: tic-incompatible response –> no tic –> no relief –> no negative reinforcement

Question 4

Describe how inhibitory control may be involved in Tourette’s Syndrome and the expression of tics and compulsions.

Answer 4

• Children with TS may exhibit increased activation through the direct pathway of the BG
• TS may lead to increased compensatory activation in inhibitory brain regions (e.g., prefrontal cortex) –> greater inhibition of fast impulsive actions

Question 5

Describe basic mechanisms of cognitive behavioral therapy for Tourette Syndrome, using your knowledge of inhibitory control and negative reinforcement.

Answer 5

Exposure with response prevention: practices inhibiting tics –> breaks the association between premonitary urges and tics

Question 6

Define “compulsion” / “compulsive”.

Answer 6

Stimulus –> impulsion –> lack of inhibition –> compulsivity –> compulsion

• compulsivity: the tendency to repeat over and over a certain kind of behavior, despite its inappropriateness, and to be able to inhibit the behavior
• compulsion: action despite conscious intent of the contrary

Question 7

Describe the principal common effect of drugs of abuse on neurotransmitters.

Answer 7

==> increased dopamine levels in the synaptic cleft in nucleus accumbens –> reward effect –> increase wanting –> positive reinforcement

Question 8

Describe how the focus changes in the reward circuit in progression from acute effects to addiction.

Answer 8

Initially, drug use increase the dopamine levels in the synaptic cleft in nucleus accumbens, reinforcing use due to immediate rewarding effects. Over time, chronic use changes the brain’s reward system, reducing its responsiveness to normal rewards and increasing sensitivity to drug-related cues. This shift leads to a pathological focus on seeking the drug over other healthy rewards, facilitating addiction.

Question 9

Describe the principal mechanism(s) of how stimulant drugs elevate dopamine levels.

Answer 9

• coke: block DAT (dopamine reuptake transporter)
• amphetamine: reverse dopmamine reuptake (vMAT, DAT)

Question 10

Describe the principal mechanism of how alcohol and opioids elevate dopamine.

Answer 10

Opiods: Inhibits GABAergic interneuron signaling by binding to mu opioid endorphin receptors –> disinhibition of dopaminergic VTA neurons–> more dopamine release

Alcohol: multiple effetcs - bind to glutamatergic neurons in nucleus accumbens (NAc) –> more DA release, but also have effects in the VTA?

Question 11

Provide an example of non-dopamine reward mechanism (neurotransmitter change).

Answer 11

The endocannabinoid system:
- modulates GABA/glutamate signaling, and thereby indirectly modulate dopamine signaling
- opioids
- alcohol

Question 12

Define positive and negative reinforcement.

Answer 12

Positive reinforcement involves increasing a behavior by presenting a rewarding stimulus after the behavior, while negative reinforcement involves increasing a behavior by removing an aversive stimulus in response to the behavior. Both are used to increase the likelihood of a behavior’s occurrence.

Question 13

Provide examples of neuroplasticity that underlies the progression from drug use to addiction.

Answer 13

• drugs induce persistent neuroplastic adaptions in midbrain DA neurons and their projections into Nac and dorsal striatum (underlie conditioning and enhanced incentive saliency to drug cues and behavioral inflexibility)
• glu system: enhanced excitability + modulation of neuroplasticity: glu input onto DA neurons in TA and into MSNs in NAc are also affected –> changes in dendritic morphology, changes in AMPA/NMDA-Rs –> LTP/LTD

==> changes in reward responsitivity that characterize addication, including a persistant risk of relapse

• in summary: drugs induce plastic changes on many levels and some of these changes are thought to underlie the transition from recreational drug use to SUDs

Question 14

Describe the main brain areas involved in drug reward and their functions in the circuit

Answer 14

The main brain areas involved in drug reward include the ventral tegmental area (VTA), nucleus accumbens (NAc), prefrontal cortex (PFC), and the extended amygdala. The VTA releases dopamine into the NAc, which reinforces drug taking and seeking behaviors. The PFC is involved in decision-making and exerting control over drug use. The extended amygdala is associated with the negative emotional states experienced during withdrawal.