Changes In Extracellular Concentrations Of Dopamine Research Articles

Cocaine‐induced changes in time course of regional cerebral blood volume and transit time as determined by dynamic MR imaging

We examined cocaine-mediated change in regional cerebral blood volume (rCBV) and mean transit time (MTT) in central brain structures of rats using functional MR imaging techniques. Changes in MTT and rCBV in animals who had previously been given cocaine depended on the length of time between the last pretreatment injection and the acute injection and seemed to parallel cocaine-mediated changes in extracellular dopamine concentrations.

Comparison of changes in extracellular dopamine concentrations in the nucleus accumbens during intravenous self-administration of cocaine or d-amphetamine

Changes in extracellular concentrations of dopamine (DA) were measured in vivo in the nucleus accumbens of the rat during intravenous self-administration of either cocaine (0.25, 0.5, 1.0mg/infusion) or d-amphetamine (0.05, 0.1, 0.2mg/infusion). Drug intake was limited to 12 self-administered infusions per session for each drug/dose combination. Changes in extra-cellular DA concentrations were measured by two different techniques: chronoamperometry in conjunction with chronically-implanted stearate-modified carbon paste electrodes, or intracerebral microdialysis with off-line analyses using high performance liquid chromatography with electrochemical detection (HPLC-ED). Significant increases in extracellular DA concentrations were observed with both in vivo techniques during self-administration of each dose of cocaine or d-amphetamine. For each drug, the magnitude of change during the first hour of the test session was comparable across doses. However, the change observed over the first 2h period, as measured by microdialysis and HPLC-ED, revealed a dose effect for cocaine, but no dose-response effect for d-amphetamine. The duration of the drug-induced elevation was increased significantly as a function of dose with both cocaine and d-amphetamine. Data from the microdialysis experiments indicated that the high dose of d-amphetamine (0.2mg/infusion) produced a significantly greater increase in extracellular DA concentrations in the nucleus accumbens than did the high dose of cocaine (1.0mg/infusion), but that comparable changes were induced by doses of 0.1mg/infusion of d-amphetamine and 1.0mg/infusion of cocaine, respectively. Each dose of both psychostimulant drugs also produced a significant decrease in dihydroxyphenylacetic acid (DOPAC) levels. The latter finding indicated that the electrochemical signal measured in these studies was not due to the oxidation of DOPAC. These results confirm that self-administration of cocaine or d-amphetamine by the rat is accompanied by a significant increase in extracellular DA concentrations in the nucleus accumbens. The fact that two different psychomotor stimulant drugs of abuse have qualitatively similar neurochemical correlates when self-administered, adds credence to the hypothesis that their reinforcing properties are related to dynamic changes in DA concentrations in the ventral striatal region of the brain.

Fluctuations in nucleus accumbens dopamine during cocaine self-administration behavior: An in vivo electrochemical study

High-speed chronoamperometry with Nafion-coated monoamine-sensitive carbon fiber electrodes was used to estimate changes in extracellular dopamine concentration in the nucleus accumbens during cocaine self-administration behavior in rats. In trained animals, time-locked biphasic fluctuations in dopamine-dependent electrochemical signal were found to accompany cocaine self-injections (0.8-0.9 mg/kg/inj). The mean signal gradually increased by the equivalent of 20-30 nM of dopamine during the 60 s preceding the injection, reached a peak value at the lever-press and decreased abruptly by about 20-30 nM for 40-60 s after the injection. This cyclic pattern was repeated with the next lever-press. The post-cocaine signal decreases were most pronounced during the first 30 min of each session, when self-administration behavior was highest (eight to 16 injections), and gradually diminished during the session. In contrast, the pre-injection signal increases became enhanced over time. Lever-presses reinforced by a double cocaine dose were followed by significantly larger and longer lasting signal decreases. These biphasic fluctuations quickly disappeared after several non-reinforced lever-presses. Although experimenter-delivered cocaine injections paced to mimic the pattern of self-administration also induced biphasic signal fluctuations, both the post-drug signal decreases and subsequent pre-injection increases were significantly smaller. It is hypothesized that the increases in signal seen in trained animals are a consequence of cocaine-induced dopamine uptake inhibition following behavior-associated dopamine cell activation. In contrast, the post-cocaine abrupt transient signal depression may be related to a decrease in mesolimbic dopamine release due to inhibition of dopamine cell activity. Signal decreases seen after self-administered procaine suggest that cocaine's local anesthetic action may contribute to this decrease in dopamine release. Additionally, while the latency of response differed somewhat, since apomorphine administration also led to a reduction in signal, autoreceptor activation may also have contributed to the cocaine-induced signal depression. That learning and behavioral mechanisms are also important determinants of the observed cocaine-induced signal changes is suggested by the signal decreases after the first non-reinforced responses, signal differences between self- and passively-administered cocaine and signal increases caused by cocaine-related cues. In light of numerous neuropharmacological studies implicating the significance of the mesolimbic dopamine system in the organization and regulation of goal-directed behaviors, these data suggest that mesolimbic dopamine system activation may mediate motivational and activational components of drug-seeking and drug-taking behavior, while the transient, reward-associated inhibition of the system may be involved in regulating these behaviors.(ABSTRACT TRUNCATED AT 400 WORDS)

Extracellular dopamine in rat striatum following uptake inhibition by cocaine, nomifensine and benztropine

A microdialysis/smallbore chromatographic system was used to monitor changes in extracellular dopamine concentration in the striatum of the rat following administration of drugs that block catecholamine uptake. Analysis of 0.5 μ1 of dialysate very 5 min showed dose-dependent elevations in extracellular dopamine following systemic administration of nomifensine (1 and 10 mg/kg), benztropine (5 and 25 mg/kg) and cocaine (3, 10 and 30 mg/kg). The order of potency in vivo was nomifensine > cocaine > benztropine. The short sampling interval allows accurate temporal profiles following pharmacological manipulations to be acquired.

5-HT; peripheral and central receptors, and function: Symposium of the British Pharmacological Society, Birmingham UK

The recent electrophysiological characterization of TH-expressing GABAergic interneurons (THINs) in the neostriatum revealed an unexpected degree of diversity of interneurons in this brain area (Ibáñez-Sandoval et al., 2010, Unal et al., 2011, 2015). Despite being relatively few in number, THINs may play a significant role in transmitting and distributing extra- and intrastriatal neuromodulatory signals in the striatal circuitry. Here we investigated the dopaminergic and cholinergic regulation of THINs in vitro. We found that the dominant effect of dopamine was a dramatic enhancement of the ability of THINs to generate long-lasting depolarizing plateau potentials (PPs). Interestingly, the same effect could also be elicited by amphetamine-induced release of endogenous dopamine suggesting that THINs may exhibit similar responses to changes in extracellular dopamine concentration in vivo. The enhancement of PPs in THINs is perhaps the most pronounced effect of dopamine on the intrinsic excitability of neostriatal neurons described to date. Further, we demonstrate that all subtypes of THINSs tested also express nicotinic cholinergic receptors. All THINs responded, albeit differentially, with depolarization, PPs and spiking to brief application of nicotinic agonists. Powerful modulation of the nonlinear integrative properties of THINs by dopamine and the direct depolarization of these neurons by acetylcholine may play important roles in mediating the effects of these neuromodulators in the neostriatum with potentially important implications for understanding the mechanisms of neuropsychiatric disorders affecting the basal ganglia.