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Past Topics: Discussion on depression, attention, and other topics from extra credit reading assignments.
Assessment Submission: Students are encouraged to submit completed assignments.
Feedback Solicitation: Instructor expresses appreciation for student feedback, emphasizing the importance of open-ended responses in guiding improvements for future semesters.

In-Class Assessments: Introduction of in-class assessments as an experimental approach this semester, seeking student feedback regarding their frequency and difficulty.
Future Adjustments: Based on feedback, the instructor is open to changing aspects of the assessments in coming semesters.

Next Topics: Class on Thursday will cover psychosis and schizophrenia; the following Tuesday, antipsychotics will be introduced.
Open Class Period: Next Thursday may be used as a review session ahead of finals.
Final Exam Details: Scheduled for Monday of finals week; will be accessible on Canvas from 12:00 AM to 11:59 PM with a time limit. Further details regarding the exam format to be provided later.

Previously Covered Content: Reviewed concepts of the reactive and reflective reward systems in the context of addiction.
Drug Addiction Progression: Adherence to stages of addiction: therapeutic use escalated to dependence, withdrawal, and relapse. Neurobiological adaptations reflect these stages.

Neurobiological Signatures: Different phases of addiction show unique neurobiological patterns as follows:
- Initial Use: As individuals begin using drugs, their reward systems adapt—specifically, dopaminergic pathways become more responsive, evidencing neuroplastic changes.
- Dependence and Withdrawal: Transition from drug use to withdrawal leads to distinct neurological responses, including hypoactivity in dopaminergic systems.

Initial Therapeutic Use to Dependence: Focus on nicotine as an example of addiction showing how it interacts with brain reward systems, specifically its action on acetylcholine and dopamine pathways.

AMPA and NMDA Receptors: Changes in the AMPA to NMDA receptor ratio following drug exposure indicate increased excitability in dopaminergic neurons.
- Electrophysiological Recording: Evidence shows increased synaptic activity in response to drug exposure.

Medium Spiny Neurons Overview: Neurons within the nucleus accumbens that process dopamine signals; their activity varies during drug administration:
- Anticipatory Neurons: Fire before reward delivery, indicating expectation of reward.
- Reinforcement Excitatory Neurons: Activate during reward delivery, reinforcing drug-seeking behavior.
- Inhibitory Neurons: Exhibit decreased excitability tied to dopamine release, influencing addiction dynamics.

Acute Withdrawal: Characterized by drastic changes in neuronal firing rates; initial hypoactivity of dopamine cells leads to feelings of anhedonia (lack of pleasure).
- Dopamine Measurements in Withdrawal: Studies illustrate variations in dopamine levels across different groups (naive, non-dependent, and dependent animals); dependent animals showed reduced dopamine signals correlating with withdrawal discomfort.

Physical Alterations in Dopamine Neurons: Evidence of dendritic spine alterations in medium spiny neurons during withdrawal; increased spine density as a compensatory mechanism when dopamine levels drop.
Human Neurobiology Adaptation Studies:
- Dopamine D2 Receptors: PET scan studies show declines in D2 receptors in individuals abstaining from drug use, a marker of altered neural circuitry post-addiction.
- Prefrontal Cortex Activity: Notable hypoactivity at rest in drug users, accompanying hyperactivity when exposed to drug-related cues, suggesting dysregulation tied to cravings and relapse behavior.

Types of Nicotinic Receptors: Main subtypes affecting the dopamine system include:
- Alpha 4 Beta 2: Higher affinity, subject to desensitization.
- Alpha 7 Homomeric: Primarily a calcium channel affecting presynaptic glutamate release.

Initial Effects of Nicotine: Activation of nicotinic receptors increases dopamine release but leads to receptor desensitization with repeated exposure.
Neuronal Adaptations: Over time, the compensatory upregulation of high-affinity nicotinic receptors on GABAergic interneurons promotes increased inhibition of dopaminergic signaling, contributing to withdrawal symptoms.

Nicotine Replacement Therapy: Such as gums and patches, providing a continuous low dose of nicotine without the harmful peaks of smoking.
Varenicline: A partial agonist for alpha 4 beta 2 receptors, offering a dual effect of stabilizing the receptor state while also lessening cravings without allowing for the full effects of nicotine.
Bupropion (Wellbutrin): Functions as a dopamine and norepinephrine reuptake inhibitor while inhibiting alpha 4 beta 2 receptor activity, increasing overall dopamine levels in withdrawal phases.

Reinforcement and Tolerance: The reinforcement experienced from nicotine decreases over time leading to increased cigarette consumption as users chase prior effects; first cigarette of the day often yields greater satisfaction due to lower receptor desensitization immediately following a period of abstinence.
Complex Interplay of Cues and Cravings: Various cues associated with smoking habits contribute significantly to ongoing cravings and relapses.