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Updated: Apr 29, 2026
Examination of Rapid Dopamine Dynamics with Fast Scan Cyclic Voltammetry During Intra-oral Tastant Administration in Awake Rats
Published on: August 12, 2015
Simultaneous intra-accumbens remifentanil and dopamine kinetics suggest that neither determines within-session
Jose A Crespo1, Katja Sturm, Alois Saria
1Department of Psychiatry, Division of Neurochemistry, Medical University Innsbruck, Austria.
Rationale:
The ultra-short-acting mu opioid agonist analgesic/anesthetic remifentanil (RMF) is extremely rapidly eliminated from blood (half-life in rats, 0.3-0.7 min). This extremely fast elimination is thought to be the main reason why RMF maintains such high rates of responding in animal operant-conditioning models of drug addiction.
Objective:
The present study investigated if such a fast elimination of RMF also occurs in the extracellular space of the brain, i.e., in the pharmacokinetic compartment that is thought to be ultimately mediating the reinforcing effect, and hence, the abuse liability of drugs.
Methods:
Nucleus accumbens (NAC) RMF and dopamine (DA) were simultaneously quantified by in vivo microdialysis followed by tandem mass spectrometry both in rats that traversed an alley to receive intravenous injections of 0.032 mg kg(-1) RMF in an operant runway procedure (contingent RMF) and in rats that passively received RMF in the runway (noncontingent RMF).
Results:
Regardless of the mode of administration (i.e., contingent or noncontingent), intra-accumbens RMF peaked in the first 10-min sample and decreased exponentially with a t(1/2) of 10.0+/-1.2 min (N=31). RMF-stimulated DA peaked in the 10-min sample immediately after the RMF peak and decreased with a time course very similar to that of RMF. Crosscorrelation of the NAC RMF and NAC DA curves showed them to be tightly synchronized. Noncontingent single-dose RMF was eliminated from the whole brain with a half-life of 1.1+/-0.2 min and from blood with a half-life of 0.3 min or less. The comparison of blood-vs-brain RMF pharmacokinetics with rat RMF self-administration behavior, either in operant runway (present study) or in lever-press-based operant-conditioning procedures, suggests that titration of blood RMF, whole-brain RMF, intra-accumbens RMF, or accumbal DA levels (assessed with the limited temporal resolution of in vivo microdialysis) does not determine a rat's decision to reemit a response during a multiple-injection drug self-administration session.
Insights
Remifentanil (RMF) is rapidly eliminated from rat brains, with a half-life of approximately 10 minutes in the nucleus accumbens. This rapid brain elimination, not blood levels, influences drug-seeking behavior in addiction models.
Area of Science:
- Neuroscience
- Pharmacology
- Addiction Research
Background:
- Remifentanil (RMF) is an ultra-short-acting opioid with rapid blood elimination (0.3-0.7 min half-life in rats).
- This rapid elimination is linked to high responding rates in animal addiction models.
Purpose of the Study:
- To investigate if remifentanil (RMF) also exhibits rapid elimination in the brain's extracellular space.
- To determine the pharmacokinetic compartment mediating the reinforcing effects and abuse liability of RMF.
Main Methods:
- Simultaneous quantification of nucleus accumbens (NAC) remifentanil (RMF) and dopamine (DA) using in vivo microdialysis and tandem mass spectrometry in rats.
- Rats received either contingent or noncontingent intravenous RMF injections in an operant runway procedure.
Main Results:
- Intra-accumbens RMF peaked within 10 minutes and had a half-life of 10.0±1.2 min, regardless of administration mode.
- RMF-stimulated DA release in the NAC mirrored RMF's elimination kinetics, showing tight synchronization.
- Whole-brain RMF elimination half-life was 1.1±0.2 min, similar to blood elimination (<0.3 min).
Conclusions:
- Remifentanil (RMF) is rapidly eliminated from the rat brain extracellular space, similar to its blood elimination.
- The study suggests that rapid brain pharmacokinetics, specifically in the nucleus accumbens, and not blood levels, are crucial for understanding RMF's reinforcing effects and abuse potential.
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