Acute Effects of Cocaine on Human Acute Effects of Cocaine on Human Brain Activity & EmotionBrain Activity & Emotion

John W. CandlerJohn W. Candler

Biology DepartmentBiology Department

Eastern Connecticut State UniversityEastern Connecticut State University

Acute Effects of Cocaine on Human Acute Effects of Cocaine on Human Brain Activity & EmotionBrain Activity & Emotion

Breiter, H.C., R.L. Gollub, R.M. Weisskoff, Breiter, H.C., R.L. Gollub, R.M. Weisskoff, et alet al. 1997. Acute . 1997. Acute effects of cocaine on human brain activity and emotion. effects of cocaine on human brain activity and emotion. NeuronNeuron. 19: 591-613.. 19: 591-613.

Cocaine Causes:Cocaine Causes:

• Profound state of addictionProfound state of addiction

• Inability to control use, despite adverse consequencesInability to control use, despite adverse consequences

• ““Reinforcing” types of behavior changesReinforcing” types of behavior changes

Previous Studies:Previous Studies:

• Examined neural pathways of addictionExamined neural pathways of addiction

• Confined to invasive animal studiesConfined to invasive animal studies

• Limited detail due to available imaging technologyLimited detail due to available imaging technology

Purpose:Purpose:

• Map dynamic patterns of brain activity in humansMap dynamic patterns of brain activity in humans

• Following cocaine infusionFollowing cocaine infusion

• Utilizing non-invasive technologyUtilizing non-invasive technology

• High resolution imaging, previously unavailableHigh resolution imaging, previously unavailable

• Provide evidence of dynamic neurological networks Provide evidence of dynamic neurological networks associated with drug induced euphoria and cravingassociated with drug induced euphoria and craving

Methods:Methods:

• 17 subjects (13 men, 4 women)17 subjects (13 men, 4 women)

• Mean age 34.5 years (Mean age 34.5 years (± 4.6 yrs)± 4.6 yrs)

• Addicted to cocaine, otherwise healthy by physical examinationAddicted to cocaine, otherwise healthy by physical examination

• No history of head traumaNo history of head trauma

Methods:Methods:

• Double-blind with saline controlsDouble-blind with saline controls

• Cocaine infusion administered (0.6mg/kg over 30sec.)Cocaine infusion administered (0.6mg/kg over 30sec.)

• Monitored 5 min. pre-infusion, 15 min. post-infusionMonitored 5 min. pre-infusion, 15 min. post-infusion

• Subjects rate the high, rush, craving, & low associated Subjects rate the high, rush, craving, & low associated with infusionwith infusion

• Evaluate brain region activity with fMRIEvaluate brain region activity with fMRI

Results: Behavioral Ratings Results: Behavioral Ratings (High vs. Rush) (High vs. Rush)

Infusion

Results: Behavioral Ratings Results: Behavioral Ratings (High vs. Craving)(High vs. Craving)

Infusion

Results: Behavioral Ratings Results: Behavioral Ratings (High vs. Low)(High vs. Low)

Infusion

Results: Brain Region ActivityResults: Brain Region Activity

• Measured Measured activityactivity using fMRI using fMRI

• Increased / decreased blood flow and oxygenationIncreased / decreased blood flow and oxygenation

• Compared fMRI data to behavioral ratingsCompared fMRI data to behavioral ratings

Results: Results: Brain Activity During “High”Brain Activity During “High”

• Short Duration ChangesShort Duration Changes• Limbic & Paralimbic RegionsLimbic & Paralimbic Regions

• Ventral TegmentumVentral Tegmentum

• Basal ForebrainBasal Forebrain

• Pontine BrainstemPontine Brainstem

• CaudateCaudate

• InsulaInsula

• Cingulate GyrusCingulate Gyrus

• Prefrontal CortexPrefrontal Cortex

Results: Results: Brain Activity During “Rush”Brain Activity During “Rush”

• Short Duration ChangesShort Duration Changes• Limbic & Paralimbic RegionsLimbic & Paralimbic Regions

• Ventral TegmentumVentral Tegmentum

• Left Basal ForebrainLeft Basal Forebrain

• CaudateCaudate

• Rt. InsulaRt. Insula

• Rt. Anterior CingulateRt. Anterior Cingulate

• Rt. Posterior CingulateRt. Posterior Cingulate

• Posterior ThalmusPosterior Thalmus

• Rt. PutamenRt. Putamen

• Lt. Posterior HippocampusLt. Posterior Hippocampus

Results: Results: Brain Activity During “low & craving”Brain Activity During “low & craving”

• Sustained Duration Sustained Duration ChangesChanges

• Nucleus AccumbensNucleus Accumbens

• Left AmygdalaLeft Amygdala

• Rt. Parahippocampal GyrusRt. Parahippocampal Gyrus

Summary: Summary: EuphoriaEuphoria

• Activity in Ventral Tegmentum, Basal Forebrain, and other regions:Activity in Ventral Tegmentum, Basal Forebrain, and other regions:

– Correlated well with euphoria ratingsCorrelated well with euphoria ratings

– VT is a major source of dopamine for NAC region VT is a major source of dopamine for NAC region

– Euphoria may be associated with Dopamine transmissionEuphoria may be associated with Dopamine transmission• As suggested by previous animal research evidenceAs suggested by previous animal research evidence

Summary: Summary: CravingCraving

• Activation in Nucleus Accumbens, Amygdala, and Hippocampus:Activation in Nucleus Accumbens, Amygdala, and Hippocampus:

– Correlated with craving responsesCorrelated with craving responses• Not a strong correlation as compared to euphoria resultsNot a strong correlation as compared to euphoria results

– Craving may not be mediated by these 2 – 3 areas alone…Craving may not be mediated by these 2 – 3 areas alone…

– Craving may reflect the numbers of activated regionsCraving may reflect the numbers of activated regions

– Suggests a distributed network of regions involved with craving Suggests a distributed network of regions involved with craving

– Further research necessary Further research necessary

Conclusions:Conclusions:

• In Humans, functional integration of circuits involved in:In Humans, functional integration of circuits involved in:– EuphoriaEuphoria

– ReinforcementReinforcement

– CravingCraving

• Future research:Future research:– Do these regions function the same way in humans as in animals?Do these regions function the same way in humans as in animals?

– HowHow do these functions produce incentive and reward? do these functions produce incentive and reward?