Functional consequences of cocaine re-exposure after discontinuation of cocaine availability

Abstract

Cocaine users exhibit a wide range of behavioral impairments accompanied by brain structural, neurochemical and functional abnormalities. Metabolic mapping studies in cocaine users and animal models have shown extensive functional alterations throughout the striatum, limbic system, and cortex. Few studies, however, have evaluated the persistence of these effects following cessation of cocaine availability. The purpose of this study, therefore, was to assess the functional effects of re-exposure to cocaine in nonhuman primates after the discontinuation of cocaine self-administration for 30 or 90 days, using the quantitative autoradiographic 2-[14C]deoxyglucose (2DG) method. Rhesus monkeys self-administered cocaine (fixed interval 3-min schedule, 30 infusions per session, 0.3 mg/kg/infusion) for 100 sessions followed by 30 (n=4) or 90 days (n=3) during which experimental sessions were not conducted. Food-reinforced control animals (n=5) underwent identical schedules of reinforcement. Animals were then re-exposed to cocaine or food for one final session and the 2DG method applied immediately after session completion. Compared to controls, re-exposure to cocaine after 30 or 90 day drug-free periods resulted in lower rates of glucose utilization in ventral and dorsal striatum, prefrontal and temporal cortex, limbic system, thalamus, and midbrain. These data demonstrate that vulnerability to the effects of cocaine persists for as long as 90 days after cessation of drug use. While there was some evidence for recovery (fewer brain areas were affected by cocaine re-exposure at 90 days as compared to 30 days), this was not uniform across regions, thus suggesting that recovery occurs at different rates in different brain systems.

The thalamus in drug addiction: from rodents to humans

“…In rhesus monkeys trained to self-administer cocaine, exposure to cocaine cues after the acquisition of drug-seeking behaviours was associated with higher metabolism in multiple regions of the thalamus, including the ventral anterior thalamus, MD thalamus, midline thalamic regions, parafascicular/centromedian nuclei and habenula [79]. Nevertheless, it is clear that this relationship is not linear as suggested by studies using exposure to cocaine cues where 30-day abstinence was associated with higher metabolism in one study [80] and decreased metabolism in another study that also showed decreased metabolism after exposure to cocaine cues after a more protracted 90-day abstinence [81].…”

Graphene–hemin hybrid nanosheets as a label-free colorimetric platform for DNA and small molecule assays

“…For many years, sensitive and selective methods have been developed for the determination of cocaine. [20][21][22] Since the aptamer of cocaine was discovered in 2000, a number of sensors based on the cocaine aptamer have been reported. 23,24 Various amplication strategies have been used to improve the sensitivity, such as rolling circle amplication (RCA), polymerase chain reaction (PCR) and so on.…”