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Z L Kruk

Publications and source records attributed to Z L Kruk.

At least 19 recordsLinked to original sources
PubMed2000

Direct effects of 3,4-methylenedioxymethamphetamine (MDMA) on serotonin or dopamine release and uptake in the caudate putamen, nucleus accumbens, substantia nigra pars reticulata, and the dorsal raphé nucleus slices.

We examined the effects of pressure ejected 3, 4-methylenedioxymethamphetamine (MDMA) from a micropipette on direct chemically stimulated release, and on electrically stimulated serotonin (5-HT) or dopamine (DA) release in the caudate putamen (CPu), nucleus accumbens (NAc), substantia nigra pars reticulata (SNr), and the dorsal raphé nucleus (DRN) brain slices of rat, using fast cyclic voltammetry (FCV). MDMA is electroactive, oxidising at +1100 mV. When the anodic input waveform was reduced from +1.4 to +1.0 volt, MDMA was not electroactive. Using this waveform, pressure ejection of MDMA did not release 5-HT or DA in brain slices prepared from any of the nuclei studied. MDMA significantly potentiated electrically stimulated 5-HT release in the SNr and DA release in CPu. In the DRN or in the NAc, MDMA was without effect on peak electrically stimulated 5-HT or DA release. The rates of neurotransmitter uptake, expressed as t(1/2), were in all cases significantly decreased after MDMA. The results indicate that MDMA, unlike (+)amphetamine, is not as a releaser of DA or 5-HT, it is a potent inhibitor of both DA and 5-HT uptake.

Amphetamine↗
PubMed1999

MK-801 interaction with the 5-HT transporter: a real-time study in brain slices using fast cyclic voltammetry.

The effects of a noncompetitive N-methyl-D-aspartate (NMDA) receptor antagonist dizocilpine ((+)-MK-801) and a competitive NMDA antagonist, (+/-)-3-2-carboxypiperazin-4-yl-propyl-1-phosphonic acid (CPP) were compared in electrically evoked 5-HT release in the brain slices incorporating the substantia nigra pars reticulata (SNr) or the dorsal raphé nucleus (DRN) using fast cyclic voltammetry (FCV). Electrical stimulation of either the SNr or the DRN with 50 pulses at frequencies greater than 10 Hz generated signals that were indistinguishable from 5-HT. In the SNr, 0.6-60 microM MK-801 concentration dependently potentiated stimulated 5-HT release. CPP 20 microM or NMDA 100 microM had no effect on 5-HT release evoked by electrical stimulation. In the SNr, 1 microM fluvoxamine or 0.6-60 microM MK-801 potentiated electrically evoked release of 5-HT. Pre-exposure to 20 microM MK-801 inhibited the enhancing effects of 1 microM fluvoxamine on electrically evoked 5-HT release in the SNr. In the DRN, the presence of 1 microM fluvoxamine or 20 microM MK-801 weakly potentiated 5-HT release. In the presence of 1 microM methiothepin (a nonselective 5-HT1-2 antagonist), 1 microM fluvoxamine or 20 microM MK-801 were equipotent in potentiating the concentration of 5-HT released in response to electrical stimulation. The T1/2 values for 5-HT release following MK-801 or fluvoxamine administration were significantly increased. Potentiation of 5-HT release by MK-801 in the SNr and the DRN and lack of effect of either CPP or NMDA on 5-HT release or uptake argues against a role for NMDA receptors in modulation of 5-HT release. Inhibition of fluvoxamine induced potentiation of 5-HT signal in the presence of MK-801 suggests that MK-801 and fluvoxamine may interact at the level of the 5-HT transporter.

Animals↗
PubMed1998

Pharmacological characterisation of dopamine overflow in the striatum of the normal and MPTP-treated common marmoset, studied in vivo using fast cyclic voltammetry, nomifensine and sulpiride.

The in vivo measurement of electrically-evoked dopamine overflow was measured for the first time in the striatum of control and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-treated common marmosets using fast cyclic voltammetry at untreated carbon-fibre microelectrodes, (7 microm, o.d.). The identity of dopamine was confirmed using electrochemical, pharmacological and histological criteria and complied with rat data from earlier studies. Dopamine overflow depended on the intensity, number of pulses, and frequency of the applied stimuli. Maximum dopamine overflow occurred using 1.0-2.0 mA, 200 micros pulse width, 150-200 pulses at 80-120 Hz stimulation of the medial forebrain bundle. Evoked dopamine overflow in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-treated marmosets showed a similar electrochemical and pharmacological profile compared to healthy controls, albeit the concentration detected was significantly reduced. The catecholamine uptake blocker, nomifensine, significantly increased the dopamine signal in control marmosets. However, in contrast, nomifensine had no significant effect on evoked dopamine overflow in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-treated marmosets. Apart from demonstrating that fast cyclic voltammetry with electrical stimulation can be reliably used to monitor dopamine overflow within the primate brain, our results describe for the first time the technical prerequisites for the fast cyclic voltammetric technique in the non-human primate brain.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗
PubMed1998

Real time measurement of stimulated dopamine release in the conscious rat using fast cyclic voltammetry: dopamine release is not observed during intracranial self stimulation.

Fast cyclic voltammetry (FCV) was used to measure real time release of electrically stimulated endogenous dopamine in the nucleus accumbens (NAc) of conscious freely moving rats for up to 17 days. The method of electrode construction, implantation, electrical stimulation and recording of changes of extracellular dopamine concentration in the conscious rat are described. Rats trained on a continuous reinforcement schedule to perform intracranial self stimulation (ICSS) were implanted with electrodes for FCV. During ICSS, no faradaic signal was observed at an electrode implanted in the NAc. Decreasing the intensity of the stimulating current abolished ICSS, increasing the stimulating current disrupted ICSS. Operator delivered electrical stimulations using currents greater than those needed for ICSS yielded dopamine signals. It is concluded that during ICSS, sufficient dopamine does not reach the extracellular fluid space to yield a faradaic signal detectable by FCV.

Animals↗
PubMed1998

Differential release of dopamine by nitric oxide in subregions of rat caudate putamen slices.

Fast cyclic voltammetry was used to measure NO and dopamine (DA) simultaneously in rat caudate putamen (CPu) slices. Analysis of electrochemical signals obtained from mixtures of DA and NO showed that subtraction of either the DA or the NO component revealed the contribution of the other component. Application of such data manipulation to signals obtained in CPu slices indicated that DA and NO components contributed to electrochemical signals. Following electrical stimulation (>1 s), site-dependent NO-like signals were observed. Pressure ejection of NMDA yielded a biphasic electrochemical signal. The first phase (lasting 10-20 s) had electrochemical characteristics of DA and was observed only during the first application of NMDA. The second phase developed more slowly, was of longer duration (1-3 min), and had electrochemical characteristics of a mixture of DA and NO. Generation of the NO-like signal by NMDA was antagonised by L-N-monomethylarginine. Pressure ejection of NO into CPu slices caused dose- and site-dependent DA release. More DA was released in the dorsolateral than in the dorsomedial CPu. Pressure ejection of DA did not generate NO. It is concluded that electrically stimulated DA release is not mediated by prior release of NO.

Animals↗
PubMed1997

Real-time measurement of stimulated 5-hydroxytryptamine release in rat substantia nigra pars reticulata brain slices.

Fast cyclic voltammetry at a carbon fibre microelectrode was used to measure 5-HT signals following electrical or chemical stimulation in rat substantia nigra pars reticulata slices. Chemical stimulation with (+)-amphetamine or veratrine gave signals which were indistinguishable from those of exogenous 5-HT. Electrical stimulation of sufficient duration gave voltammetric signals which were characteristic of 5-HT. Release of dopamine was not detected following either chemical or electrical stimulation. The 5-HT signals were attenuated by TTX and enhanced by fluvoxamine. It was not possible to demonstrate regulation of 5-HT release in the SNr by 5-HT1B autoreceptors using CGS 12066A or methiothepin. Signal following electrical stimulation were not enhanced by either benztropine or GBR12909, or modified in the presence of either quinpirole or sulpiride. We conclude that 5-HT release can be detected voltammetrically in the SNr; 5-HT release is likely to be from axon terminals, but somatodendritic DA release could not be detected.

Animals↗
PubMed1996

Comparison of somatodendritic and axon terminal dopamine release in the ventral tegmental area and the nucleus accumbens.

Fast cyclic voltammetry at a carbon fibre microelectrode was used to measure dopamine release following electrical or chemical stimulation in rat brain slices incorporating either the ventral tegmental area or the core region of the nucleus accumbens. Electrical or chemical stimulation gave clear voltammetric signals which corresponded to dopamine; less dopamine was released in the ventral tegmental area than in the nucleus accumbens. In contrast to the nucleus accumbens, electrically stimulated dopamine release in the ventral tegmental area was not sensitive to tetrodotoxin, was not modified by the presence of dopamine uptake inhibitors, or agonist or blockers acting at dopamine D2 autoreceptors.

Amphetamine↗
PubMed1996

The role of ventral tegmental dopamine neurons in locomotor sensitization following quinpirole or (+)-amphetamine: ex vivo voltammetric evidence.

Behavioural sensitization to the locomotor stimulating effects of (+)-amphetamine or quinpirole was induced in rats by intermittent drug administration. Following expression of sensitization, locomotor activity scores on day 9 were: vehicle 87 +/- 9, (+)-amphetamine 1441 +/- 227 and quinpirole 2078 +/- 214. Electrically stimulated dopamine release was measured on day 12 in ventral tegmental slices using fast cyclic voltammetry. Dopamine release was significantly elevated in the (+)-amphetamine- and quinpirole-treated groups when compared to vehicle-treated controls over a wide range of stimulation frequencies (5-200 Hz) and pulses (1-200). Quinpirole (1 microM) in the perfusion fluid attenuated dopamine release following 40-pulse, 200-Hz electrical stimulation, by 31.6 +/- 2.8% in the ventral tegmental area of the vehicle-treated group, by 14.8 +/- 5.6% in the (+)-amphetamine-treated group and 8 +/- 7.3% in the quinpirole-treated group. This study shows that dopamine release is increased in the ventral tegmental area following sensitization with either a direct or indirectly acting dopamine agonist. The findings that dopamine release was elevated at all stimulation frequencies in sensitized animals, and that quinpirole only attenuated this release at the highest stimulation frequency, would suggest that in addition to D2 autoreceptor subsensitivity, other mechanisms contribute to the enhanced release of dopamine in these animals.

Animals↗
PubMed1996

Real-time effects of N-methyl-D-aspartic acid on dopamine release in slices of rat caudate putamen: a study using fast cyclic voltammetry.

The functional role of N-methyl-D-aspartic acid (NMDA) glutamate receptors in the real-time regulation of single electrical pulse (1 p)-stimulated endogenous dopamine release was investigated in slices of rat caudate putamen using fast cyclic voltammetry at a carbon fibre electrode. In the presence of Mg2+, 20 microM NMDA had a weak effect on background signals but did not affect 1 p-stimulated dopamine release. Removal of Mg2+ increased the background and doubled 1 p-stimulated dopamine release. In the absence of Mg2+, 20 microM NMDA caused a transient "release" of dopamine and decreased the background signal. The 1 p-stimulated dopamine release was subsequently reduced. In the presence of 1 microM (+/-)-3-(2-carboxypiperazin-4-yl)-propyl-1-phosphonic acid (CPP), superfusion with 20 microM NMDA did not cause a transient "release" of dopamine, and 1 p-stimulated dopamine release was not subsequently attenuated. In the presence of 1 microM tetrodotoxin, 1 p-stimulated dopamine release was abolished, but 20 microM NMDA still caused a transient "release" of dopamine. Removal of Ca2+ from the artificial CSF abolished 1 p-stimulated dopamine release and resulted in a decline in the baseline but did not affect dopamine "release" when 20 microM NMDA was added. The dopamine release-inducing effect of 20 microM NMDA was less pronounced in sites in the caudate putamen where dopamine release increased with frequency of electrical stimulation (hot spots) than in sites where there was little frequency-dependent dopamine release (cold spots). Subsequent 1 p-stimulated dopamine release was less attenuated in cold spots than in hot spots. We conclude that in the absence of Mg2+, NMDA induces release of dopamine by acting at CPP-sensitive NMDA receptors in a Ca(2+)-independent manner. This transient release depletes dopamine from a storage site from which dopamine is released by 1 p electrical stimulation. These real-time observations of the effects of NMDA on electrical stimulus-independent and -dependent dopamine release may explain the apparently conflicting observations of the effects of NMDA on dopamine release made in previous studies. They also indicate that dopamine release and storage are heterogeneous at different sites in the rat caudate putamen.

Animals↗
PubMed1995

Influences of neuronal uptake and D2 autoreceptors on regulation of extracellular dopamine in the core, shell and rostral pole of the rat nucleus accumbens.

Fast cyclic voltammetry in rat brain slices containing the nucleus accumbens, was used to examine the regulation of the extracellular concentration of electrically stimulated dopamine overflow in the core, shell and rostral pole. One microM (-)-sulpiride, significantly increased dopamine overflow in all 3 regions but only when the duration of stimulation was greater than 500 ms. One microM cocaine, significantly potentiated dopamine overflow in all 3 regions following all patterns of stimulation. In the presence of 1 microM cocaine, superfusion with 1 microM (-)-sulpiride did not result in a further increase in dopamine overflow at any frequency of stimulation in the rostral pole, but significant increases in dopamine overflow were observed after stimulation with 20 pulses at 10 or 20 Hz in the core or shell; the degree of potentiation was greater in the shell than core. Quinpirole inhibited single pulse stimulated dopamine overflow in a concentration dependent manner (maximum inhibition (100%) in all regions) but was significantly less potent in the rostral pole than in the core or shell. Increasing the number of pulses to 2 or 4 pulses at 50 Hz resulted in a shift of the quinpirole dose-response curve to the right in all regions and in the rostral pole, a significant reduction in the maximum inhibition of dopamine overflow to both stimulation parameters. In the shell a significant reduction in maximum inhibition was only seen with 4 pulses at 50 Hz stimulation, whereas in the core there was no change in the maximum inhibitory effect of quinpirole. Neuronal uptake and D2 autoreceptor activity contribute to regulation of the extracellular concentration of dopamine in core, shell and rostral pole. The relative importance of either uptake or autoreceptor control is region and stimulus dependent.

Animals↗
PubMed1995

Parametric analysis of the effects of cocaine and cocaine pretreatment on dopamine release in the nucleus accumbens measured by fast cyclic voltammetry.

Fast cyclic voltammetry was used to measure dopamine (DA) release in the nucleus accumbens of anaesthetized rats, in response to electrical sine-wave stimulation of the ventral tegmental area. Voltammetric signals followed increases in either frequency (50-100 Hz), intensity (50-100 microA) or duration (0.5-5.0 s) of the stimulus. Cocaine administration (10 mg/kg) preferentially increased DA release by weak electrical stimuli. Cocaine pretreatment (3 x 10 mg/kg, two weeks earlier) preferentially increased DA release by stronger stimuli, and the effects of acute cocaine were potentiated in these animals. The effects of increasing stimulus duration conformed to first order kinetics. Cocaine pretreatment selectively increased the kinetic parameter representing maximal release, while acute cocaine administration preferentially decreased the parameter representing the stimulus duration eliciting half maximal release. The lack of statistical interaction between these two effects suggests that sensitization of the response to acute cocaine by cocaine pretreatment may simply reflect an increase in the size of the releasable pool of DA.

Animals↗
PubMed1995

Effects of amphetamine on carrier-mediated and electrically stimulated dopamine release in slices of rat caudate putamen and nucleus accumbens.

The effects of (+)-amphetamine on carrier-mediated and electrically stimulated dopamine release were investigated using fast cyclic voltammetry in rat brain slices incorporating the nucleus accumbens, and in the caudate putamen. In the caudate putamen, dopamine release either increased with increasing frequency of local electrical stimulation (hot spots) or did not increase significantly (cold spots); dopamine release increased with increasing frequency of electrical stimulation in the nucleus accumbens. Local pressure application of (+)-amphetamine from a micropipette caused dopamine efflux at all sites examined, and this was not affected by sulpiride, indicating that efflux of dopamine caused by (+)-amphetamine is not regulated by dopamine D2 autoreceptors. (+)-Amphetamine reduced single-pulse electrically stimulated dopamine release at all sites; sulpiride reversed this decrease, indicating that endogenous dopamine released by (+)-amphetamine activates dopamine D2 autoreceptors. In nucleus accumbens and hot spots, (+)-amphetamine did not affect 20-pulse 50-Hz-stimulated dopamine release, whereas in cold spots it potentiated 20-pulse 50-Hz-stimulated dopamine release. We conclude that (+)-amphetamine modifies electrically stimulated dopamine release by uptake inhibition or by indirect activation of D2 autoreceptors; the precise mechanism is determined by site and duration of electrical stimulation.

Amphetamine↗
PubMed1995

Biphasic inhibition of stimulated endogenous dopamine release by 7-OH-DPAT in slices of rat nucleus accumbens.

1. Fast cyclic voltammetry was used to investigate the effect of 7-OH-DPAT (7-hydroxy-N,N-di-n-propyl-2-aminotetralin), a putative D3 receptor agonist, on electrically stimulated endogenous dopamine release in slices of rat nucleus accumbens. 2. 7-OH-DPAT inhibited single pulse stimulated dopamine release in a concentration-dependent manner with a maximum inhibition of 95.5%. Analysis of concentration-response curves to 7-OH-DPAT showed that they were biphasic, with the high affinity component contributing 18.0% to the total inhibition and the low affinity component 77.5%. 7-OH-DPAT exhibited a 560 fold selectivity between the high and low affinity components (0.015 nM compared to 8.4 nM). 3. Concentration-response curves to the non-selective D2/D3 agonist, apomorphine, were monophasic. The maximum inhibition was 93.1% and the EC50 value 82 nM. 4. The selective D2 antagonist, haloperidol (30 nM), antagonized the low affinity component of the concentration-response cuve to 7-OH-DPAT whilst the high affinity component was essentially unaffected. The pKB values calculated for the high and low affinity components were 7.89 and 9.45 respectively. 5. In conclusion, these results demonstrate that 7-OH-DPAT inhibits stimulated dopamine release by acting at two different sites. Furthermore, the results are consistent with the hypothesis that the high and low affinity components of the concentration-response curve to 7-OH-DPAT may reflect activation of functional D3 and D2 release-regulating autoreceptors respectively. However, the possibility that the biphasic nature of the curve may reflect different subtypes of the D2 receptor cannot be excluded.

Animals↗
PubMed1994

A quantitative comparison on the effects of benztropine, cocaine and nomifensine on electrically evoked dopamine overflow and rate of re-uptake in the caudate putamen and nucleus accumbens in the rat brain slice.

Fast cyclic voltammetry has been used to study the relative importance of neuronal dopamine (DA) uptake and D2 autoreceptor stimulation on the control of the extracellular concentration of electrically evoked DA in rat brain slices containing aCPu and NAc. The degree of potentiation of DA overflow by benztropine, cocaine and nomifensine was always greater in the aCPu than in the NAc. Although EC50 values for the uptake blockers in the NAc were lower than in the aCPu, they were only significantly lower for 1 p with benztropine. One microM (-)-sulpiride, significantly potentiated DA overflow evoked by 20 p/20 Hz in both regions. In the presence of either 1 microM cocaine or 1 microM nomifensine, sulpiride further potentiated DA overflow in the NAc but not in the aCPu. The results indicate that in brain slices containing the aCPu, neuronal uptake is the main mechanism of controlling extracellular concentrations of DA due to electrical stimulation. Whilst in the NAc both uptake and D2 autoreceptor activation are important control mechanisms. The rate of removal of DA from the extracellular medium was not significantly different in the two regions but was decreased in the presence of (-)-sulpiride. This indicates that D2 receptors have a modulating effect on the DA neuronal uptake mechanism.

Animals↗
PubMed1994

Effects of 21 days treatment with fluoxetine on stimulated endogenous 5-hydroxytryptamine overflow in the rat dorsal raphe and suprachiasmatic nucleus studied using fast cyclic voltammetry in vitro.

Changes in the extracellular concentration of 5-HT evoked by electrical stimulation of brain slices containing either dorsal raphe nucleus (DRN) or suprachiasmatic nucleus (SCN) from rats treated for 21 days with fluoxetine (5 mg/kg; i.p.) or water were monitored using fast cyclic voltammetry (FCV). Stimulated 5-HT overflow was enhanced significantly in both brain regions after 21 days treatment with fluoxetine but there was no change in the half time for re-uptake (t1/2). Concentration response curves for inhibition of electrically stimulated 5-HT overflow by 8-OH-DPAT (5-HT1a receptor agonist) or RU24969 (5-HT1b receptor agonist) in the DRN or SCN respectively were obtained in slices prepared from both groups of animals. There was a significant shift to the right in the dose-response curve for RU24969 in the SCN in fluoxetine treated animals but a shift to the left for the dose-response curve for 8-OH-DPAT in the DRN. These data suggest that down regulation of the 5-HT1b autoreceptors occurs in an axon terminal region (SCN) but that there is a sensitisation of 5-HT1a autoreceptor mechanisms controlling 5-HT overflow in the DRN.

8-Hydroxy-2-(di-n-propylamino)tetralin↗
PubMed1994

Differential action of (+)-amphetamine on electrically evoked dopamine overflow in rat brain slices containing corpus striatum and nucleus accumbens.

1. The effects of (+)-amphetamine on electrically evoked dopamine overflow were examined in the rat brain slice containing either anterior caudate putamen (aCPu) or nucleus accumbens (NAc), by fast cyclic voltammetry. 2. (+)-Amphetamine (1 microM) caused a time-dependent increase in the extracellular concentration of dopamine ([dopamine]ex) due to displacement of dopamine from terminal sites. After a 40 min superfusion, [dopamine]ex in the aCPu was 0.617 +/- 0.117 microM and in the NAc was 0.270 +/- 0.04 microM. Pretreatment with (-)-sulpiride (1 microM) did not affect this action of (+)-amphetamine. 3. (+)-Amphetamine (1 microM) exhibited a complex and time-dependent effect on electrically stimulated dopamine overflow, evoked by 1p, 4p/10 Hz and 20p/20 Hz. 4. In the aCPu, (+)-amphetamine (1 microM) resulted in attenuation of dopamine overflow due to 1p and 4p/10 Hz but potentiation of dopamine overflow to 20p/20 Hz. (-)-Sulpiride (1 microM) prior to (+)-amphetamine (1 microM) reversed the attenuation of dopamine overflow evoked by 1p and 4p/10 Hz but had no significant effect on dopamine overflow evoked by 20p/20 Hz. 5. (+)-Amphetamine (1 microM) potentiated dopamine overflow in the NAc to all three stimuli. (-)-Sulpiride (1 microM) prior to (+)-amphetamine (1 microM), resulted initially, in a further potentiation of overflow, followed by a time-dependent attenuation of dopamine overflow to all three stimuli. 6. t1/2, the rate of removal of [dopamine]ex following electrical stimulation was not significantly different in the aCPu and NAc for any of the stimulation conditions. After a 40 min superfusion with (+)-amphetamine (1 MicroM), t1/2 for ip, 4p/10 Hz and 20p/20 Hz was significantly increased in both the aCPuand NAc, the increase in t1/2 being significantly greater in the aCPu than in the NAc.7. In conclusion, this study indicates that the dopamine displacement and uptake inhibitory actions of(+ )-amphetamine result in complex and differential effects on electrically evoked dopamine overflow in the aCPu and NAc.

Amphetamine↗
PubMed1992

Regional differences in evoked dopamine efflux in brain slices of rat anterior and posterior caudate putamen.

Fast cyclic voltammetry using carbon fibre microelectrodes in rat brain slices, was used to investigate regional differences in electrically-evoked dopamine (DA) efflux at 10 different sites in the anterior caudate putamen (aCPu) and 10 sites in the posterior caudate putamen (pCPu). For each site DA overflow was evoked by both single pulse (1P) stimulation and by trains of 25 pulses applied at a frequency of 50 Hz (25P/50 Hz). Peak DA efflux evoked by 1P was about 58% greater in the aCPu (0.19 mumol/l DA) than in the pCPu (0.12 mumol/l DA), but showed no mediolateral variation in either region. Peak DA efflux evoked by 25P/50 Hz relative to 1P efflux also varied between the two regions; the aCPu contained predominantly low ratio (25P/50 Hz: 1P) sites ranging from 1.47 to 3.71, whereas in the pCPu these ratios were higher, ranging from 2.73 to 9.40, and were particularly high in the dorsomedial region of the pCPu. Efflux detected in low ratio sites of the aCPu showed little dependence on the frequency (10 to 500 Hz), or the number of pulses (5 to 20) in a train. By contrast DA efflux evoked in high ratio sites of the pCPu responded in a pulse and frequency dependent manner, the maximum ratio (approximately 8 times 1P) being at 20P/20 Hz. Interestingly the frequency response relationship obtained in the pCPu resembled the profile observed in the nucleus accumbens (NAc). Voltammetric evidence and experiments with selective reuptake blockers indicated that only DA was measured in our studies and 5-HT did not significantly contribute to the frequency dependent pattern of efflux detected in high ratio sites of the pCPu, where striatal 5-HT concentrations are highest. Experiments with the selective D2 receptor antagonists metoclopramide or (-)sulpiride revealed that under our experimental conditions, DA efflux in the aCPu was not modulated by DA autoreceptor activation. By contrast, autoreceptor modulation did occur in high ratio sites of the pCPu at stimulations lasting longer than approximately 1000 ms. These observations support the concept that the caudate putamen is heterogeneously organised with respect to the frequency characteristics of evoked DA release. The factors controlling frequency dependent release under these conditions may be a function of A10 innervation, since high ratio release sites occur in areas where the density of such innervation is greatest, for example, the dorsomedial pCPu. This is supported by the observation that high ratio release sites are also found in the NAc, which receives dopaminergic fibres predominantly from an A10 region.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗