Motivation Gone Awry

Chiba

Most Slides Courtesy of Dr. George Koob

Neurocircuitry of Addiction

Derived from: Koob G, Everitt, B and Robbins T, Reward, motivation, and addiction. In: Squire LR, Berg D, Bloom FE, du Lac S, Ghosh A, Spitzer NC (Eds.), Fundamental Neuroscience, 3rd edition, Academic Press, Amsterdam, 2008, pp. 987-1016.

Key Common Neuroanatomical Structures in Addiction

Nucleus Accumbens and Central Nucleus of the Amygdala — Forebrain structures involved in the rewarding effects of drugs of abuse and drives the binge intoxication stage of addiction. Contains key reward neurotransmitters: dopamine and opioid peptides

Extended Amygdala — Composed of central nucleus of the amygdala, bed

nucleus of the stria terminalis, and a transition zone in the medial part of the nucleus accumbens. Contains “brain stress” neurotransmitter, corticotropin releasing factor that controls hormonal, sympathetic, and behavioral responses to stressors, and is involved in the anti-reward effects of drug dependence

Medial Prefrontal Cortex — neurobiological substrate for “executive function”

that is compromised in drug dependence and plays a key role in facilitating relapse. Contains major glutamatergic projection to nucleus accumbens and amygdala

Neurocircuitry of Addiction

Derived from: Koob G, Everitt, B and Robbins T, Reward, motivation, and addiction. In: Squire LR, Berg D, Bloom FE, du Lac S, Ghosh A, Spitzer NC (Eds.), Fundamental Neuroscience, 3rd edition, Academic Press, Amsterdam, 2008, pp. 987-1016.

From: Koob GF, Alcohol Clin Exp Res, 2003, 27:232-243.

Positive and Negative Reinforcement- Definitions

Positive Reinforcement — defined as the process by which presentation of a stimulus (drug) increases the probability of a response (non dependent drug taking paradigms).

Negative Reinforcement —defined as a process by which removal of an aversive stimulus (negative emotional state of drug withdrawal) increases the probability of a response (dependence-induced drug taking)

Stages of the Addiction Cycle

Animal Models for the Different Stages of the Addiction Cycle

•  Animal Models for the Binge/Intoxication Stage1. Oral or intravenous drug self-administration2. Brain stimulation reward3. Place preference

•  Animal models for the Withdrawal/Negative Affect Stage1. Brain stimulation reward2. Place aversion

•  Animal Models for the Transition to Addiction1. Dependence-induced drug taking2. Escalation in drug self-administration with prolonged access 3. Drug taking despite aversive consequences

•  Animal Models for the Preoccupation/Anticipation (“Craving”) Stage1. Drug- induced reinstatement2. Cue- induced reinstatement3. Alcohol Deprivation Effect4. Stress- induced reinstatement

Neurochemical Circuitry in Drug Reward

From: Koob GF, Clin Neurosci Res, 2005, 5:89-101.

Converging Acute Actions of Drugs of Abuse on the Ventral Tegmental Area and Nucleus Accumbens

From: Nestler EJ, Nat Neurosci, 2005, 8:1445-1449.

CNS Actions of Corticotropin-Releasing Factor (CRF)

Major CRF-Immunoreactive Cell Groups and Fiber Systems in the Rat Brain

From: Swanson LW, Sawchenko PE, Rivier J and Vale W, Neuroendocrinology, 1983, 36:165-186.

Positive Reinforcement

Negative Reinforcement

Non-dependent Dependent

Negative Reinforcement

Positive Reinforcement

Brain Arousal-Stress System Modulation in the Extended Amygdala

Pain, Emotions, and the Amygdala

From: Neugebauer V, Li W, Gird GC and Han JS, The Neuroscientist, 2004, 10:221-234.