Fluctuations in extracellular dopamine and DOPAC levels in nucleus accumbens septi (NAS) were monitored in 1-min microdialysis samples taken from rats engaged in intravenous cocaine self-administration. For four rats the dose per injection was fixed at 2.0 mg/kg; for four others the dose per injection was varied irregularly, from one response to the next, between three levels (0.5, 1.0 and 2.0 mg/kg). Regardless of the dosing regimen, extracellular dopamine levels were tonically elevated by 200-800% within the cocaine self-administration periods, fluctuating phasically within this range between responses. In the fixed dose condition, the phasic increases following each injection (and the phasic decreases preceding them) averaged approximately 50% of the mean tonic elevation. Phasic fluctuations in dopamine levels remained time-locked to lever-presses even when response rate was irregular, because of the variable dose condition. In the variable dose condition greater increases in dopamine and longer inter-response times followed injections of the higher doses; dopamine fluctuations were consistent with the multiple-infusion pharmacokinetics of cocaine. DOPAC levels showed a slow tonic depression during cocaine self-administration, but individual injections were not associated with discernible phasic fluctuations of DOPAC. These data are consistent with the hypothesis that falling dopamine levels trigger successive responses in the intravenous cocaine self-administration paradigm, but inconsistent with the notion that extracellular dopamine levels are depleted at the times within sessions when the animal initiates drug-seeking responses.

Extracellular dopamine and DOPAC (3,4-dihydroxyphenylacetic acid) levels in nucleus accumbens were sampled by microdialysis and quantified with high-performance liquid chromatography during intravenous heroin self-administration sessions in rats. Dopamine levels in 10 and 20 min samples were elevated following the first injection of each session, reaching a plateau of elevation within the first two or three injections and falling back toward baseline only when drug access was terminated. Elevations were in the range of 150-300% when unit dosages of 0.05-0.2 mg/kg were given. Increasing the work requirement from FR-1 to FR-10 did not appear to alter the degree of elevation of dopamine levels, and dopamine levels fell during extinction while lever-pressing rates increased 20-fold. While animals compensated for unit dose changes between 0.05 and 0.2 mg/kg/injection, adjusting their response rate such that the same hourly drug intake and the same asymptotic dopamine levels were maintained across these conditions, at 0.4 mg/kg/injection hourly drug intake and asymptotic dopamine levels were elevated beyond the levels sustained by the lower doses. These findings confirm that self-administered doses of intravenous heroin are sufficient to activate the mesolimbic dopamine system and suggest that significant heroin "craving" can emerge when dopamine levels are still moderately elevated, long before the development of dopamine depletion associated with opiate withdrawal.

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ImportanceInternational efforts are being made towards a person-centred care (PCC) model, but there are currently no standardised mechanisms to measure and monitor PCC at a healthcare system level. The use of metrics to measure PCC can help to drive the changes needed to improve the quality of healthcare that is person centred.ObjectiveTo develop and validate person-centred care quality indicators (PC-QIs) measuring PCC at a healthcare system level through a synthesis of the evidence and a person-centred consensus approach to ensure the PC-QIs reflect what matters most to people in their care.MethodsExisting indicators were first identified through a scoping review of the literature and an international environmental scan. Focus group discussions with diverse patients and caregivers and interviews with clinicians and experts in quality improvement allowed us to identify gaps in current measurement of PCC and inform the development of new PC-QIs. A set of identified and newly developed PC-QIs were subsequently refined by Delphi consensus process using a modified RAND/UCLA Appropriateness Method. The international consensus panel consisted of patients, family members, community representatives, clinicians, researchers and healthcare quality experts.ResultsFrom an initial 39 unique evidence-based PC-QIs identified and developed, the consensus process yielded 26 final PC-QIs. These included 7 related to structure, 16 related to process, 2 related to outcome and 1 overall global PC-QI.ConclusionsThe final 26 evidence-based and person-informed PC-QIs can be used to measure and evaluate quality incorporating patient perspectives, empowering jurisdictions to monitor healthcare system performance and evaluate policy and practice related to PCC.