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J B Justice

Publications and source records attributed to J B Justice.

At least 37 records · Page 2Linked to original sources
PubMed1997

6-Hydroxydopamine lesion of ventral pallidum blocks acquisition of place preference conditioning to cocaine.

In parallel with nucleus accumbens (NAS), ventral pallidum (VP) also receives a dopaminergic projection from the ventral tegmental area (VTA). The present study examined the involvement of this mesopallidal dopaminergic system in the action of cocaine. In the first experiment, the effect of cocaine injections on VP dopamine was examined by microdialysis. Intraperitoneal (i.p.) injections of cocaine 5-20 mg/kg dose-dependently increased the extracellular dopamine level in VP 2.5-4.5-fold. In addition, intra-VP perfusion of 20 microM cocaine induced a 12-fold increase of dopamine locally. The second experiment examined the role of VP dopamine in cocaine-induced conditioned place preference (CPP) and locomotor activation. Rats received bilateral intra-VP injections of 3-4 microg 6-OHDA or ascorbic acid vehicle in 0.5 microl volume. Tissue assays indicated that the 6-OHDA-lesioned rats had significantly lowered dopamine concentration in VP, but not in NAS or striatum. As a group, 6-OHDA lesions blocked the development of CPP to 5 mg/kg cocaine but not to 10 mg/kg cocaine. However, rats with more than 60% depletion in VP dopamine did not develop CPP to cocaine at either dose. Preference for the cocaine-paired side correlated significantly with dopamine concentration in VP, but not in NAS or striatum. It was concluded that VP dopamine may play a critical role in the initial rewarding effect of cocaine. 6-OHDA lesions also blocked locomotor activation induced by 5 mg/kg cocaine but had no effect on 10 mg/kg cocaine-induced locomotion. Dopamine concentration in VP did not correlate with the locomotor activation response to cocaine at either dose. These findings further establish the involvement of the mesopallidal dopaminergic system in the action of cocaine.

Animals↗
PubMed1997

Dissociation of locomotor and conditioned place preference responses following manipulation of GABA-A and AMPA receptors in ventral pallidum.

1. This study examined the roles of GABAergic and glutamatergic neurotransmission in ventral pallidum (VP) in conditioned place preference and locomotor activity. 2. Picrotoxin (0.1 microgram), a GABA antagonist, and (+/-)alpha-amino-3-hydroxy-5-methylisoxazole-4-propionate (AMPA; 0.14 microgram), a non-NMDA glutamatergic agonist, were injected bilaterally into VP through implanted cannulae. 3. Both drugs produced a robust increase in locomotion, but neither produced conditioned place preference. 4. These results suggest a dissociation of locomotor activity and reward at the level of ventral pallidum. In addition, it was argued that the GABAergic projection from nucleus accumbens to ventral pallidum may not be involved in the processing of reward initiated from dopaminergic activation in nucleus accumbens.

Animals↗
PubMed1996

Regulation of dopamine uptake in rat striatal tissue by NMDA receptors as measured using rotating disk electrode voltammetry.

Rotating disk electrode (RDE) voltammetry was used to examine the effect of N-methyl-D-aspartate (NMDA) on the initial velocity of dopamine (DA) uptake in suspensions of rat striatal tissue. Transport velocities were determined by measuring the rate of clearance of 2 microM DA added to the tissue suspension. NMDA (200 microM) was found to increase the initial velocity of DA transport from 548 +/- 28 to 803 +/- 63 pmol/s per g tissue (mean +/- SEM; P < 0.005). The increase was reversed by the competitive NMDA antagonist AP5, and thus appears to be receptor-mediated. In a separate experiment, lower concentrations of NMDA (20-100 microM) yielded a high correlation (r = 0.96; P < 0.05) of velocity versus concentration. Kainic acid (10 microM) also was found to increase the initial rate of uptake, from 505 +/- 34 to 702 +/- 71 pmol/s per g (P < 0.05). The results of this study indicate that the rate of DA uptake in the striatum can be modulated in vitro by presynaptic ionotropic glutamate receptors.

2-Amino-5-phosphonovalerate↗
PubMed1996

Human norepinephrine transporter kinetics using rotating disk electrode voltammetry.

Rotating disk electrode (RDE) voltammetry is applied to the measurement of the transport of the catecholamine neurotransmitters norepinephrine (4-(2-amino-1-hydroxyethyl)-1,2-benzenediol, NE) and dopamine (3,4-dihydroxyphenethylamine, DA) in suspensions of LLC-NET cells, a line of porcine kidney cells expressing the human norepinephrine transporter (hNET). Initial rate of transport was assessed by following the initial decrease in neurotransmitter after its addition to the cell suspension, as measured by the decrease in oxidation current at +0.45 V vs Ag/AgCl. The initial rate of norepinephrine uptake was saturable, with Vmax and KM of 197 +/- 17 amol min-1 cell-1 and 1.64 +/- 0.46 microM, respectively. The RDE method also allows observation of outward transport (efflux) of the DA or NE previously taken up by the cells. Outward transport was induced by the addition of either d-amphetamine (d-AMPH) or p-tyramine (4-hydroxyphenethylamine, p-TYR), which are also substrates for the NE transporter. The technique was also used to monitor accelerated NE uptake by cells preloaded with p-TYR, a phenomenon distinguishing carriers from channels. Together, these findings document the utility of RDE for the nonisotopic measurement of neurotransmitter influx and efflux from transfected mammalian cells.

Animals↗
PubMed1996

Effect of general microdialysis-induced depletion on extracellular dopamine.

Continuous sampling by microdialysis induces a general depletion of all low molecular weight materials around the microdialysis probe. The effect of this depletion on the estimation of extracellular dopamine (DA) concentration was evaluated for various degrees of depletion. The basal level of DA in the striatum of male Wistar rats was estimated by the zero net flux method at six different flow rates ranging form 0.3 to 1.6 microL/min. The extracellular DA concentrations in the striatum of male rats measured by this method were found not to differ significantly from one flow rate to another (p > 0.05) with a mean of 6.5 nM +/- 0.11. These finding suggest that the estimation of extracellular dopamine by quantitative microdialysis is independent of the flow rate and that the depletion of other extracellular substances around the probe has no effect on the determination of the extracellular concentration of dopamine.

Animals↗
PubMed1996

Conditioned place preference and locomotor activation produced by injection of psychostimulants into ventral pallidum.

The ventral pallidum (VP) is often viewed as an output structure of the nucleus accumbens septi (NAS). However, VP, like NAS, receives a dopaminergic input from the ventral tegmental area. These experiments investigated some behavioral effects of microinjection into VP of drugs which enhance dopaminergic transmission. Injection of 25 micrograms dopamine or 5-10 micrograms amphetamine into VP produced hypermotility. In contrast, injection of 12.5-50 micrograms cocaine initially suppressed, then increased, activity. Injection of 100 micrograms cocaine only produced hypomotility in the 1-h period examined. The hypomotility following cocaine seemed to be a local anesthetic effect, because it was mimicked by 50-200 micrograms procaine. Procaine did not, however, produce subsequent hypermotility. Conditioned place preference (CPP) was produced by 10 micrograms amphetamine and 50 micrograms cocaine but not 100 micrograms procaine. We conclude that injection of cocaine into VP unlike similar injections into NAS, produces CPP. These results support the idea of an involvement of dopamine in VP in reward and locomotor activation, independent of dopamine in NAS. The use of intracerebral injections of cocaine is complicated, however, by an apparent local anesthetic effect of the drug.

Amphetamine↗
PubMed1996

Quantitative microdialysis of serotonin and norepinephrine: pharmacological influences on in vivo extraction fraction.

The present study was designed to investigate the potential influence of various neuronal processes including uptake, release and metabolism, on the in vivo microdialysis extraction fraction (Ed) of serotonin (5HT) and norepinephrine (NE). Paroxetine administration decreased the Ed of 5HT in the nucleus accumbens from 24 +/- 3 to 18 +/- 0.2% (p < 0.05). Similarly, desipramine infusion reduced the NE Ed from 35 +/- 2 to 26 +/- 1% (p < 0.05). However, perfusion with pargyline or tetrodotoxin had no effect on the Ed of either 5HT or NE. Perfusion with agonists for the 5HT, alpha-adrenergic, D2 and histamine receptors had no effect on the Ed of 5HT. In the same manner, perfusion with the alpha-adrenergic agonists, methoxamine or clonidine, did not affect the Ed of NE. These data are in agreement with experimental results obtained for dopamine in the nucleus accumbens and the theory of quantitative microdialysis which predicts that only changes in the rate of clearance will change Ed of monoamines. These results suggest that, like DA, changes in the Ed for 5HT or NE are indicative of changes in the reuptake of these neurotransmitters. The results also indicate that pharmacological agents which do not affect uptake have no effect on the extraction fraction.

Animals↗
PubMed1996

Differential effects of delta- and mu-opioid receptor antagonists on the amphetamine-induced increase in extracellular dopamine in striatum and nucleus accumbens.

The specific opioid receptor antagonist naloxone attenuates the behavioral and neurochemical effects of amphetamine. Furthermore, the amphetamine-induced increase in locomotor activity is attenuated by intracisternally administered naltrindole, a selective delta-opioid receptor antagonist, but not by the irreversible mu-opioid receptor antagonist beta-funaltrexamine. Therefore, this research was designed to determine if naltrindole would attenuate the neurochemical response to amphetamine as it did the behavioral response. In vivo microdialysis was used to monitor the change in extracellular concentrations of dopamine in awake rats. Naltrindole (3.0, 10, or 30 micrograms) or vehicle was given 15 min before and beta-funaltrexamine (10 micrograms) or vehicle 24 h before the start of cumulative dosing, intracisternally in a 10-microliters volume, while the rats were lightly anesthetized with methoxyflurane. Cumulative doses of subcutaneous d-amphetamine (0.0, 0.1, 0.4, 1.6, and 6.4 mg/kg) followed pretreatment injections at 30-min intervals. Dialysate samples were collected every 10 min from either the striatum or nucleus accumbens and analyzed for dopamine content by HPLC. Amphetamine dose-dependently increased dopamine content in both the striatum and nucleus accumbens, as reported previously. Naltrindole (3.0, 10, and 30 micrograms) significantly reduced the dopamine response to amphetamine in the striatum. In contrast, 30 micrograms of naltrindole did not modify the dopamine response to amphetamine in the nucleus accumbens. On the other hand, beta-funaltrexamine (10 micrograms) had no effect in the striatum but significantly attenuated the amphetamine-induced increase in extracellular dopamine content in the nucleus accumbens. These data suggest that delta-opioid receptors play a relatively larger role than mu-opioid receptors in mediating the amphetamine-induced increase in extracellular dopamine content in the striatum, whereas mu-opioid receptors play a larger role in mediating these effects in the nucleus accumbens.

Amphetamine↗
PubMed1996

Locomotor response to novelty does not predict cocaine place preference conditioning in rats.

Previous studies have demonstrated that rats showing a strong locomotor response to a novel environment have a greater locomotor response to psychostimulant drugs and more rapidly acquire intravenous self-administration of amphetamine. In this report, we examined whether these high-responder (HR) rats would develop place-preference conditioning with cocaine more readily than low-responder (LR) rats. Neither group of rats developed conditioned place preference for cocaine, 2.5 mg/kg, intraperitoneally (IP). Both groups of rats developed conditioned place preference for cocaine, 5.0 and 15 mg/kg, IP. However, we could not find any evidence of enhanced conditioning in the HR rats. HR rats did show a greater locomotor response to cocaine, 15 mg/kg, IP, and the locomotor response of HR and LR rats to cocaine correlated with their response to a novel environment. We conclude that using the place-preference procedure, HR and LR rats do not differ in the rewarding effect of cocaine.

Animals↗
PubMed1996

Locomotor response to novelty does not predict cocaine place preference conditioning in rats.

Previous studies have demonstrated that rats showing a strong locomotor response to a novel environment have a greater locomotor response to psycho-stimulant drugs and more rapidly acquire intravenous self-administration of amphetamine. In this report, we examined whether these high-responder (HR) rats would develop place-preference conditioning with cocaine more readily than low-responder (LR) rats. Neither group of rats developed conditioned place preference for cocaine, 2.5 mg/kg, intraperitoneally (IP). Both groups of rats developed conditioned place preference for cocaine, 5.0 and 15 mg/kg, IP. However, we could not find any evidence of enhanced conditioning in the HR rats. HR rats did show a greater locomotor response to cocaine, 15 mg/kg, IP, and the locomotor response of HR and LR rats to cocaine correlated with their response to a novel environment. We conclude that using the place-preference procedure, HR and LR rats do not differ in the rewarding effect of cocaine.

Animals↗
PubMed1995

Increased sensitivity to cocaine place-preference conditioning by septal lesions in rats.

Rats bearing electrolytic lesions of medial septum and sham-operated controls were trained on cocaine place-preference in a 3-compartment apparatus. Cocaine was paired with a white or a black compartment. An unbiased design was used, in which cocaine was paired with the preferred side in half the animals and with the unpreferred side in the other half. Two low doses of cocaine HCl were used: 2.5 and 5.0 mg/kg. Only two pairings of drug with environment were used to minimize the influence of drug sensitization. Rats with septal lesions, but not controls, showed preference conditioning to the black side at 2.5 mg/kg; lesioned and control animals showed similar conditioning to the black side at 5.0 mg/kg. Lesioned animals could not be conditioned to the white side at either dose. This was attributed to a drug-induced enhancement of a previously described increased reactivity to brightness following septal lesions. Controls conditioned to either side at 5.0 mg/kg. It was concluded that septal lesions lowered the cocaine dose required for preference conditioning, consistent with reports that such damage enhances some behavioral effects of psychostimulants.

Animals↗
PubMed1995

Naloxone reduces the neurochemical and behavioral effects of amphetamine but not those of cocaine.

The specific opioid receptor antagonist naloxone modifies the effects of amphetamine in a wide variety of behavioral paradigms. Naloxone also attenuates the amphetamine-induced increase in extracellular dopamine in the brain of rats. Therefore, these experiments were designed to replicate the neurochemical and behavioral interactions between naloxone and amphetamine, and to extend these observations to interactions between naloxone and cocaine. Microdialysis was performed on adult male rats of Sprague-Dawley descent. Rats were pretreated with a subcutaneous injection of 5.0 mg/kg naloxone or vehicle, which was followed 30 min later by cumulative doses of subcutaneous d-amphetamine (0.0, 0.1, 0.4, 1.6, 6.4 mg/kg) or intraperitoneal cocaine (0, 3, 10, 30, 56 mg/kg) at 30 min intervals. The microdialysis probes were perfused at a flow rate of 0.6 microliter/min with artificial cerebrospinal fluid. Dialysate samples were collected every 10 min from either the nucleus accumbens or striatum and analyzed for dopamine content by high-performance liquid chromatography (HPLC). Locomotor activity (photobeam breaks) was monitored simultaneously with the collection of dialysate samples. Amphetamine and cocaine dose-dependently increased extracellular dopamine in both the nucleus accumbens and striatum. Naloxone pretreatment significantly reduced the amphetamine-induced increase in extracellular dopamine in both brain regions and also attenuated the increase in locomotor activity elicited by amphetamine. Naloxone pretreatment had no effect, however, on the cocaine-induced increase in extracellular dopamine or locomotor activity. These findings suggest that endogenous opioid systems play a role in mediating the neurochemical and behavioral effects of amphetamine, but not those of cocaine.

Amphetamine↗
PubMed1995

Fluctuations in nucleus accumbens dopamine concentration during intravenous cocaine self-administration in rats.

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.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1995

Quantitative microdialysis of neuropeptide Y.

The feasibility of using the difference method of quantitative microdialysis to measure neuropeptide Y (NPY) was evaluated in vitro and in vivo. The accuracy of this method was tested in vitro under steady-state conditions for 3 test solutions containing known concentrations of NPY. The estimated concentrations of NPY were 1.2 +/- 0.6, 3.7 +/- 0.9, and 15.1 +/- 0.7 pg/microliter (mean +/- SEM) in agreement with the actual concentrations of NPY in the test solutions which were 1.1 +/- 0.8, 4.6 +/- 0.6, and 14.6 +/- 0.5 pg/microliter (mean +/- SEM of solution samples), respectively. The responsiveness of the estimated NPYext measure to changes in the external concentration of NPY was also evaluated in vitro. An accurate estimate of NPYext was obtained within the first sampling period (within 15 min) after a 2-3-fold increase in the test solution concentration of NPY and within 2-3 sampling periods (15-45 min) in response to a 2-3-fold decrease in the test solution concentration of NPY. In vivo, the estimated basal concentration of NPY in dialysis samples from probes in the medial basal hypothalamus of anesthetized female rats (n = 4) was 4.0 +/- 1.6 pg/microliters and increased to 9.5 +/- 0.3 pg/microliter during K+ stimulation. Relative recovery was 22% in vivo under steady-state conditions and ranged from 14% to 30% during dynamic conditions. These results demonstrate that the difference method of quantitative microdialysis accurately estimates picomolar concentrations of NPY in vitro, and is sufficiently sensitive to detect basal and increasing concentrations of NPY in vivo.

Animals↗
PubMed1994

Effect of tetrodotoxin and potassium infusion on microdialysis extraction fraction and extracellular dopamine in the nucleus accumbens.

The effects of tetrodotoxin (TTX) and K+ perfusion on extracellular DA concentration (DAext) and extraction fraction (also known as relative recovery or Ed) were studied using a method for quantitative microdialysis under transient conditions. TTX administered through the microdialysis probe decreased DAext with no effect on Ed. Perfusion with high K+ increased DAext, with no initial effect on Ed. However, a decrease in Ed was observed under prolonged depolarization. These data provide further evidence that Ed may change over the course of drug administration. This method of quantitative microdialysis is a reliable means for measuring changes in DAext independently of possible changes in microdialysis probe efficiency.

Animals↗
PubMed1994

Temporal response of microdialysis probes to local perfusion of dopamine and cocaine followed with one-minute sampling.

The temporal response of microdialysis probes in vivo was followed with 1-min sampling. The response under four conditions was examined: in vitro sampling of dopamine (DA), in vitro perfusion of DA, in vivo perfusion of DA, and in vivo perfusion of cocaine. The temporal response of the probe in a stirred solution at 37 degrees C for both sampling mode and perfusion mode was determined using a flow rate of 1.6 microL/min. As expected, the rate of gain or loss of DA in these two cases rapidly stabilized. The in vivo response to a step change in perfusate concentration was also examined. The rate of loss of DA into the tissue rapidly reached a steady state so that the dialysate DA concentration stabilized within 2 min. To examine the in vivo response of DA to a step change in drug concentration, dialysis probes in the striata of anesthetized rats were perfused with artificial cerebrospinal fluid interchanged with 20 microM cocaine. The increase in DA caused by its uptake inhibition by cocaine rapidly reached a maximum level in 2-4 min and then gradually decreased. After the cocaine was removed, the dialysate concentration of DA fell rapidly with some tailing, suggesting the presence of residual cocaine in the tissue. These results suggest that relatively fast changes in DA levels in tissue can be followed by microdialysis probes. The rapid stabilization also suggests that the DA concentration profile does not extend very far from the probe.

Animals↗
PubMed1994

Individual differences in schedule-induced and conditioned behaviors.

Previous experiments have shown that subjects which exhibit a high locomotor response to novelty (HR) also show a greater locomotor response to psychomotor stimulants than subjects which have a low locomotor response to a novel environment (LR). The current experiments were designed to examine in more detail the behavioral differences between HR and LR rats in non-drug paradigms. In the first experiment HR rats acquired schedule-induced polydipsia (SIP) more readily than LR rats. Panel pressing to gain access to the food pellets, however, was greater in LR rats compared to HR rats, especially after stable levels of SIP had been attained. In the second experiment one group of rats were fed daily after a 30-min period in photocell-cages (food conditioning; FC) while a control group was fed in the home-cage (non-conditioned; NC). FC subjects developed heightened locomotor activity in anticipation of feeding in the initial 30 min in the test-cage compared to NC rats. This anticipatory locomotor activity developed more rapidly and to a greater level in HR rats than in LR rats. The concentrations of dopamine, dihydroxyphenylacetic acid, homovanillic acid, serotonin, 5-hydroxyindoleacetic acid, and norepinephrine were determined at the completion of behavioral testing in both the food conditioned and non-conditioned rats. The food conditioned experiment showed that variations in both the dopaminergic and serotoninergic systems may underlie individual differences in behavioral responsiveness. However, no clear pattern of neurochemical differences emerged. The current set of experiments have demonstrated differences between HR and LR rats in non-drug related paradigms and that HR rats appear to show a greater motivational excitement induced by periodic food delivery than LR rats.

Animals↗