Footshock stress can reinstate cocaine-seeking behavior through a central action of the stress-associated neurohormone corticotropinreleasing factor (CRF). Here we report (1) that footshock stress releases CRF in the ventral tegmental area (VTA) of the rat brain, (2) that, in cocaine-experienced but not in cocaine-naive rats, this CRF acquires control over local glutamate release, (3) that CRF-induced glutamate release activates the mesocorticolimbic dopamine system, and (4) that, through this circuitry, footshock stress triggers relapse to drug seeking in cocaine-experienced animals. Thus, a long-lasting cocaine-induced neuroadaptation, presumably at the level of glutamate terminals in the VTA, appears to play an important role in stress-induced relapse to drug use. Similar neuroadaptations may be important for the comorbidity between addiction and other stress-related psychiatric disorders.
Initiation of cocaine self-administration in rats was associated with release of glutamate in the ventral tegmental area (VTA). The glutamate release was transient, despite continued cocaine intake. Similar glutamate release was seen in rats earning, for the first time, unexpected saline rather than expected cocaine. VTA glutamate release was not seen in similarly trained rats earning saline instead of cocaine for the 13th time. VTA glutamate release was also seen in similarly trained rats that received yoked rather than earned cocaine injections on test day. VTA glutamate release was not seen in a group of rats that had never earned cocaine but had received yoked injections during the training period. Glutamate release was also not seen in a group of rats that received yoked injections but had no previous experience with cocaine. VTA GABA levels did not fluctuate during any aspect of cocaine seeking. Blockade of VTA glutamate receptors appeared to attenuate the rewarding effects of intravenous cocaine injections and blocked almost completely the conditioned responding normally seen during extinction trials. These findings indicate that VTA glutamate release is a conditioned response dependent on an associative process and is not a simple consequence of previous cocaine exposure. The findings implicate glutamate as at least one of the sources of VTA signals from reward-associated environmental stimuli.
This study presents clinical expert consensus on how to manage concerning behaviors among patients on LTOT. Future research is needed to investigate how implementing these management strategies would impact patient outcomes, practice and policy.
Across the USA, morbidity and mortality from substance use are rising as reflected by increases in acute care hospitalisations for substance use complications and substance-related deaths. Patients with substance use disorders (SUD) have long and costly hospitalisations and higher readmission rates compared to those without SUD. Hospitalisation presents an opportunity to diagnose and treat individuals with SUD and connect them to ongoing care. However, SUD care often remains unaddressed by hospital providers due to lack of a systems approach and addiction medicine knowledge, and is compounded by stigma. We present a blueprint to launching an interprofessional inpatient addiction care team embedded in the hospital medicine division of an urban, safety-net integrated health system. We describe key factors for successful implementation including: (1) demonstrating the scope and impact of SUD in our health system via a needs assessment; (2) aligning improvement areas with health system leadership priorities; (3) involving executive leadership to create goal and initiative alignment; and (4) obtaining seed funding for a pilot programme from our Medicaid health plan partner. We also present challenges and lessons learnt.
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