The Koob Lab is currently researching the neurobiology of addiction and stress:

Addiction

Studies on the neurobiology of addiction continue to explore the  role of neurochemical systems in the extended amygdala in the neuroadaptations associated with the transition from drug taking to drug dependence that is an integral part of the development of addiction.  Significant efforts are continuing to be made in the development of animal models for excessive drug intake and charting the changes in motivated behavior associated with excessive drug intake.  Previous work has established that prolonged access to cocaine can produce progressive increases in drug intake that are paralleled by decreases in reward function.  This escalation is paralleled also by a loss of sensitization to the locomotor-activating effects of cocaine, a prediction consistent with an opponent process homeostatic/allostatic view and opposite to that of an incentive sensitization view of addiction.  Escalation in drug intake is accompanied by increased sensitivity to the blockade of cocaine self-administration by a mixed dopamine D1/D2 receptor antagonist and increased sensitivity to a corticotropin-releasing factor-1 (CRF1) antagonist.  These results suggest that the reward dysregulation associated with extended access to drugs of abuse, such as cocaine, that leads to addiction may depend on  neuroadaptive changes in both dopamine (a reward transmitter) and CRF (a brain stress neurotransmitter) systems.

Studies with animal models of heroin dependence have revealed similar neuropharmacological adaptations to chronic administration of opioids.  Chronic opioid exposure increases heroin self-administration in rats, and this increase can be blocked selectively by a cannabinoid CB1 receptor antagonist.  A CRF1 antagonist effectively blocked the development of place aversion to precipitated opioid withdrawal.  These studies suggest that excessive exposure to opioids can produce some of the same neuroadaptive changes in the brain observed with excessive access to other drugs of abuse.

In the domain of medications development for drug addiction, animal models for excessive drinking of alcohol continue to be developed that will be useful for identifying compounds for potential clinical development.  The excessive drinking associated with alcohol dependence can be exacerbated by intermittent repeated withdrawal from chronic alcohol exposure.  Work with highly selective CRF2 agonists have shown that the CRF2 system may have potential in blocking excessive drinking associated with dependence and the anxiogenic-like effects of alcohol withdrawal.  Given that stressor exposure is a major stimulus for relapse in human alcoholics, these data suggest a potential novel role for the CRF2 system in relapse prevention.

The conceptual framework suggesting that the neurochemical changes in reward and stress neurotransmitter systems lead to an allostatic change in motivated behavior has continued to be developed and refined.  Consistent with a role for self-medication of emotional states in humans with drug addiction, the allostatic view holds that individuals, through genetic vulnerability or environmental events, may use drugs in an attempt to return to a state of motivational homeostasis.  Because of hysteresis in the neuroadaptational capabilities of the brain motivational systems, however, such individuals defend an allostatic state rather than a homeostatic state.  Further refinement of this hypothesis is the possibility that taking the drugs themselves can either produce the allostatic state or exaggerate pre-existing genetic/environment vulnerability.

Neuropeptides and stress

Studies continue to be directed at exploring the functional significance of members of the CRF brain stress neurotransmitter system.  Human urocortin 2, a selective agonist for the CRF2 receptor, decreased feeding and drinking in the rat but did not alter locomotor activity or produce malaise.  This is in contrast to a CRF1 agonist that reduced food intake but produced locomotor activation, anxiogenic-like effects, and malaise.  Restricted feeding in a rodent model produced prolonged anxiolytic-like effects that persisted beyond normalization of food intake.  These results broaden the functional selectivity of the actions of the brain CRF/urocortin systems and provide a rich substrate for future studies for the exploration of the pathophysiology of stress and appetite disorders.