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Biomedical subjects

J B Justice

Publications and source records attributed to J B Justice.

At least 55 records · Page 3Linked to original sources
PubMed1994

Individual differences in behavior following amphetamine, GBR-12909, or apomorphine but not SKF-38393 or quinpirole.

Subjects that respond more to a novel environment show a greater locomotor response to drugs of abuse such as cocaine and amphetamine. The current study was performed to examine differences between high (HR) and low (LR) responding rats to a novel environment following administration of amphetamine, a selective dopamine uptake blocker (GBR-12909), a nonselective dopamine agonist (apomorphine), and selective dopamine D1 and D2/D3 agonists. A behavioral checklist and a rating scale were used to determine the behavioral arousal caused by administration of amphetamine (0, 0.5, 2.0, and 8.0 mg/kg), GBR-12909 (0, 1.25, 5.0, and 20.0 mg/kg), apomorphine (0, 0.1, 0.3, and 1 mg/kg), SKF 39393 (0, 2.5, 10, and 40 mg/kg), or quinpirole (0, 0.05, 0.5, and 5.0 mg/kg). The five drugs produced behavioral activation profiles distinct from each other. Following amphetamine administration, both HR and LR subjects showed dose dependent increases in behavioral arousal. The behaviors primarily affected were sniffing, locomotor activity, rearing, and oral activity. HR rats showed a greater overall behavioral response to amphetamine administration compared with LR rats and there were differences in specific behaviors between the two groups. Following GBR-12909 administration, all subjects showed dose dependent increases in sniffing, locomotor activity, and rearing. Differences between HR and LR were observed in sniffing, locomotor activity, and rearing behaviors. HR and LR both showed dose dependent increases in behavior following apomorphine administration. HR showed greater behavioral activation after apomorphine than LR.(ABSTRACT TRUNCATED AT 250 WORDS)

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗
PubMed1994

Effects of cocaine microinjections into the nucleus accumbens and medial prefrontal cortex on schedule-induced behaviour: comparison with systemic cocaine administration.

The effects of cocaine HCl infusions into either the nucleus accumbens (NACC) or medial prefrontal cortex (PFC) were compared on the performance of schedule-induced polydipsia (SIP) and related behaviours. Food-deprived rats were exposed to a fixed-time 60-s schedule of food delivery in daily 30-min sessions until stable levels of behaviour were obtained (14 days). Rats were then bilaterally infused with cocaine into either the NACC or PFC via chronically indwelling guide cannulae. Each subject received a sequence of five cocaine infusions (0, 12.5, 25, 50, 100 micrograms) according to a Latin Square design. For comparison, following these intracranial infusions each rat received a sequence of five IP injections of cocaine (0, 2.5, 5, 10, 20 mg/kg) also in a counterbalanced order. NACC and PFC infusions of cocaine and IP cocaine dose-dependently reduced SIP. Cocaine infusions into the NACC, but not the PFC, increased locomotor activity but the characteristic temporal profile of locomotor activity during SIP was retained. IP cocaine also increased locomotor activity in a dose-dependent manner, but the temporal profile of activity was flattened following 20 mg/kg cocaine. NACC and PFC infusions of cocaine had little effect on the total number of panel presses to gain access to the food pellets, but did slightly decrease the high rates of responding immediately prior to the pellet delivery. IP cocaine increased the total number of panel presses at the higher doses, mainly by increasing the low rates of responding. The effects of cocaine infusions into the PFC were behaviourally the most selective, as they reduced SIP without having substantial effects either on locomotor activity or panel pressing.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1994

Assessment of the relative contribution of peripheral and central components in cocaine place conditioning.

A balanced place conditioning paradigm was used to assess the contribution of peripheral and central factors mediating place conditioning induced by cocaine HCl. The first experiment was conducted to examine changes in locomotor activity and extracellular dopamine (DA) concentrations in the nucleus accumbens (NACC) following intraperitoneal (IP) injections of cocaine HCl (15 mg/kg) or cocaine methiodide (19.6 mg/kg). IP cocaine HCl significantly increased locomotor activity and extracellular NACC DA, whereas IP cocaine methiodide failed to increase either locomotor activity or extracellular DA in the NACC. In the second experiment, IP cocaine HCl (15 mg/kg) induced a significant conditioned place preference; however, neither IP procaine HCl (25 or 50 mg/kg) nor IP cocaine methiodide (4.9, 9.8, or 19.6 mg/kg) induced preferences for the drug-paired compartment. In the third experiment, intracerebroventricular (ICV) infusions of cocaine HCl (25 micrograms/2 microliters) or cocaine methiodide (1 or 5 micrograms/2 microliters) induced significant place conditioning for the drug-paired compartment. These results suggest place conditioning induced by cocaine HCl is mediated centrally and that the local anaesthetic properties alone do not contribute to this effect to any significant degree.

Animals↗
PubMed1994

The effect of inhibition of synthesis, release, metabolism and uptake on the microdialysis extraction fraction of dopamine.

The present study was designed to determine the effects that synthesis, release, metabolism and uptake have on the in vivo extraction fraction (relative recovery) of dopamine (DA) in the nucleus accumbens of the rat. The extraction fraction and extracellular concentration of DA were established for rats that were perfused with artificial cerebrospinal fluid (aCSF) with or without substances inhibiting synthesis (100 microM alpha-methylparatyrosine (alpha-MPT)), release (1 microM tetrodotoxin (TTX)), uptake (1 microM, 20 microM cocaine or 1 microM GBR-12909) or metabolism (100 microM tropolone or 100 microM pargyline) with DA concentrations ranging from 0 to 200 nM. Inhibiting synthesis with alpha-MPT or release with TTX had no effect on the extraction fraction of DA. Inhibiting intracellular or extracellular metabolism with pargyline or tropolone, respectively, did not cause any changes in the extraction fraction. However, inhibiting uptake with 20 microM cocaine or 1 microM GBR-12909 decreased the extraction fraction by one-third and one-half, respectively. These results provide evidence that uptake is the primary neuronal process affecting the extraction fraction of DA in the nucleus accumbens and indicate that the extraction fraction may be useful as an index of DA uptake in vivo.

Animals↗
PubMed1994

Quantitative approaches to in vivo brain microdialysis.

The microdialysis technique has been widely used for the study of extracellular chemical events in various tissues. Until recently, however, little was known about the sampling characteristics of dialysis probes in vivo. The purpose of this review is to describe several theoretical models of in vivo microdialysis that consider both the diffusional resistances encountered in vivo and the effects of various active processes, such as metabolism, release and uptake, and transport across the blood brain barrier. The relevance of the models to practical in vivo microdialysis experiments is discussed. Several microdialysis techniques that quantitatively estimate extracellular analyte concentrations are also reviewed. These techniques are discussed in relation to the theoretical models, together with a discussion of the experimental factors that affect in vivo microdialysis experiments.

Animals↗
PubMed1994

Individual locomotor response to novelty predicts selective alterations in D1 and D2 receptors and mRNAs.

Rats that have a greater locomotor response to novelty (high responders, HR) have differences in measures of presynaptic dopamine transmission compared to low responders (LR) to a novel environment, including altered dopamine release and behavioral response to indirect dopamine agonists. This study examined the role of three dopamine terminal fields, the nucleus accumbens, striatum, and medial prefrontal cortex, in differences between HR and LR. In the first experiment, dopamine was infused directly into the nucleus accumbens (0, 3, 10, and 30 micrograms/side) or the striatum (0, 10, 30, and 100 micrograms/side). HR showed a greater behavioral response to both the 3 and 30 micrograms/side doses infused into the nucleus accumbens compared to LR. No differences between HR and LR were revealed by dopamine infusion into the striatum. In the second experiment, radioligand binding assays were performed to determine if differences exist between high and low responder rats in the Bmax and/or KD of radiolabeled antagonist ligands for the dopamine D1 and/or D2 receptors. There were fewer D2 binding sites in the nucleus accumbens and fewer sites in the striatum in HR compared to LR. High responders showed a greater Bmax for D1 binding sites in the nucleus accumbens than LR. No differences in number of binding sites for D1 receptors were observed between HR and LR in the striatum. No differences between HR and LR in D2 or D1 receptor binding were observed in the medial prefrontal cortex. There were no differences in KD for any of the dopamine receptors in the regions examined.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1993

Quantitative microdialysis under transient conditions.

A microdialysis method is described which allows for the quantitative determination of extracellular analyte concentration under transient conditions. The method provides the extracellular concentration and the in vivo probe recovery as a function of time. The technique is based on the method for steady-state conditions but differs in the use of a between-group rather than a within-group design. Following cocaine and amphetamine administration, a significantly greater increase in extracellular DA was found than was estimated from the dialysate using conventional microdialysis methods. The discrepancy is due to microdialysis probe recovery decreasing concurrently with the increase observed in extracellular DA following cocaine and amphetamine injections. The method estimates the extracellular concentration independently of any changes in recovery.

Amphetamine↗
PubMed1993

Perfusate serotonin increases extracellular dopamine in the nucleus accumbens as measured by in vivo microdialysis.

The effects of local application of serotonin (5-HT) on extracellular levels of dopamine (DA) in the nucleus accumbens (N. ACC) were assessed using in vivo microdialysis. At a perfusate flow rate of 0.3 microliter/min the baseline dialysate concentration of DA was 2.1 +/- 0.7 nM (mean +/- S.E.M.; n = 5) and significantly increased to 142 +/- 18%, 220 +/- 47% and 332 +/- 35% of baseline when 0.1 microM, 0.2 microM and 0.4 microM concentrations of 5-HT were included in the perfusate. Perfusate 5-HT concentrations below 0.1 microM had no effect on dialysate DA. The in vivo dialysis efficiency for 5-HT was found to be 39 +/- 12%, and thus the concentrations of 5-HT reaching the extracellular space at the surface of the dialysis membrane were estimated to be 40, 80 and 160 nM for the 0.1, 0.2 and 0.4 microM 5-HT perfusates, respectively. The serotonin-induced increase in dialysate DA was attenuated by co-perfusion of 0.4 microM 5-HT with 4 microM concentrations of pindolol (a relatively non-specific 5-HT1 antagonist; 151 +/- 7% vs. 332 +/- 35% baseline dialysate DA for 5-HT/antagonist and 5-HT-only perfusates, respectively), LY 53,857 (a specific 5-HT2 antagonist; 130 +/- 17% vs. 332 +/- 35%) and MDL 7222 (a specific 5-HT3 antagonist; 143 +/- 19% vs. 332 +/- 35%).(ABSTRACT TRUNCATED AT 250 WORDS)

3,4-Dihydroxyphenylacetic Acid↗
PubMed1993

Environmental and pharmacological sensitization: effects of repeated administration of systemic or intra-nucleus accumbens cocaine.

The effects of repeated systemic or intra-nucleus accumbens cocaine administration on locomotor activity were examined for environmental dependence. Repeated IP administration of cocaine (15 mg/kg) for 5 days in the context of a given environment increased the locomotor response to a subsequent IP cocaine challenge in that environment. However, there were no differences in the locomotor response to a subsequent IP cocaine challenge in the test chamber in subjects which had received prior repeated IP administration of cocaine in the home-cage. In a second experiment, cocaine (100 micrograms/side) was infused into the nucleus accumbens (NACC) daily for 5 days. This repeated administration produced increases in locomotor activity to subsequent intra-NACC cocaine infusions that were environmentally independent. In contrast to the effects of repeated IP cocaine administration, subjects which received administration of vehicle, acute cocaine, or repeated cocaine in the NACC did not differ following an IP cocaine challenge. The results from these experiments indicate that increases in the response to IP cocaine following repeated IP administration are in part environmentally dependent. Moreover, repeated intra-NACC cocaine infusions increase the responsiveness of the NACC to subsequent intra-NACC cocaine. However, local activation of the NACC alone does not appear to be adequate to produce sensitization to systemically administered cocaine.

Animals↗
PubMed1993

Quantitative microdialysis of neurotransmitters.

Microdialysis methods for the quantitative determination of the extracellular concentration of neurotransmitters are described for basal and transient conditions. Measurements of dopamine (DA) in the nucleus accumbens and striatum of the rat are used as examples. The factors affecting microdialysis recovery of neurotransmitters are reviewed. Computer simulation is used to examine the effect of release and uptake on microdialysis recovery. Several new applications of microdialysis are suggested.

Animals↗
PubMed1993

Co-administration of the D2 antagonist pimozide inhibits up-regulation of dopamine release and uptake induced by repeated cocaine.

To investigate the hypothesis that the D2 dopamine (DA) receptor regulates DA uptake, as well as release, in the nucleus accumbens (N ACC), rats were pretreated for 10 days with either the selective D2 antagonist pimozide (1.0 mg/kg, i.p.) or vehicle, followed 3 h later by either cocaine (20 mg/kg, i.p.) or saline. On day 11, a microdialysis method was performed in which various DA concentrations (0, 10, and 20 nM DA) were perfused through the dialysis probe to characterize the diffusion of DA through tissue to and from the microdialysis probe (recovery). This diffusion of DA has been shown to be sensitive to changes in release and uptake. Pimozide pretreatment was shown to attenuate significantly a cocaine-induced increase in the in vivo recovery of DA (p < 0.01). The in vivo recovery for the vehicle/cocaine group was 47 +/- 4%, whereas the in vivo recovery for the pimozide/cocaine group was 31 +/- 3%. There was no difference between the pimozide/cocaine and control groups (pimozide/saline, 26 +/- 2%; vehicle/saline, 26 +/- 3%). In vitro probe calibrations indicated no significant difference in probe efficiencies between groups. These data suggest that the D2 receptor is capable of modulating uptake as well as release of DA in the N ACC of the rat.

Analysis of Variance↗
PubMed1993

Serotonin and dopamine sensitization in the nucleus accumbens, ventral tegmental area, and dorsal raphe nucleus following repeated cocaine administration.

The present study was designed to examine the effects of chronic cocaine administration on the extracellular response of serotonin (5-HT) and dopamine (DA) to a peripheral cocaine injection using in vivo brain microdialysis in awake rats. Two different dual probe preparations were used: One group of animals had guide cannulae aimed at the ventral tegmental area (VTA) and nucleus accumbens (N ACC) and a second group of animals had guide cannulae aimed at the dorsal raphe nucleus (DRN) and N ACC. Rats from both groups were given daily injections of either cocaine (20 mg/kg i.p.) or saline (0.9%; 0.05 ml/kg i.p.) for 10 consecutive days. On day 11, baseline dialysate levels of DA, 5-HT, dihydroxyphenylacetic acid, and 5-hydroxyindoleacetic acid were obtained from either the N ACC and VTA or the N ACC and DRN, followed by a 10 mg/kg i.p. cocaine injection and an additional 150 min of dialysate sampling. The percent baseline increases of both 5-HT and DA were significantly higher in the N ACC, VTA, and DRN of animals that received daily injections of cocaine compared with saline controls (p < 0.05, in each region). Maximum dialysate 5-HT concentrations after cocaine challenge were significantly higher in the N ACC and VTA (p < 0.05) and DRN (p < 0.01) of chronically treated animals compared with saline controls. Maximum dialysate DA concentrations were significantly higher in the N ACC and DRN (p < 0.05) of chronically treated animals compared with saline controls. There was no significant difference between acute and chronic animals in the maximum dialysate DA concentration from the VTA after cocaine challenge.(ABSTRACT TRUNCATED AT 250 WORDS)

3,4-Dihydroxyphenylacetic Acid↗
PubMed1992

6-Hydroxydopamine lesions of the medial prefrontal cortex fail to influence cocaine-induced place conditioning.

This study investigated the involvement of medial prefrontal cortex (mPFC) dopamine in cocaine place conditioning using a totally balanced place conditioning design. Presynaptic dopamine terminals of the mPFC were lesioned by bilaterally infusing the selective neurotoxin 6-hydroxydopamine (6-OHDA). These lesions significantly depleted dopamine (-83%) and norepinephrine (-70%) in the mPFC but there were no significant reductions in either the nucleus accumbens or in the caudate-putamen compared with sham-operated controls. Furthermore, serotonin levels were not affected in any of the brain regions investigated. These lesions failed to attenuate place conditioning induced by the intraperitoneal (i.p. 10 mg/kg) administration of cocaine when compared to sham lesioned controls. In addition, there were no significant differences in spontaneous locomotor activity between the two groups during the preconditioning phase or the test phase. These results suggest that 6-OHDA lesions which produced profound depletions of dopamine and norepinephrine in the mPFC did not alter the rewarding efficacy of cocaine as measured by the place conditioning paradigm.

Animals↗
PubMed1992

Individual differences in basal and cocaine-stimulated extracellular dopamine in the nucleus accumbens using quantitative microdialysis.

The current experiment examined the role of nucleus accumbens (NACC) dopamine in individual differences. Subjects were divided into high responders (HR) and low responders (LR) based on their locomotor response to a novel environment. HR rats were subjects which had a locomotor response to novelty in the upper third of the population screened and LR rats in the bottom third of the population. A new method of microdialysis was then used that allowed determination of the extracellular dopamine concentration. This was accomplished by adding various dopamine concentrations (0.0, 5.0 and 20.0 nM) to the perfusate. The concentration of dopamine in the dialysate was subsequently determined. The difference in the dialysate and perfusate dopamine was regressed on the perfusate dopamine. The regression yielded the in vivo recovery and the extracellular concentration. HR rats exhibit a 250% higher basal dopamine concentration (6.45 +/- 1.01 nM, n = 6) than LR rats (2.58 +/- 0.16 nM, n = 7). The in vivo microdialysis recovery was used to estimate the extracellular dopamine following cocaine challenge (15 mg/kg) in the two groups. Following i.p. cocaine administration, HR rats had both a greater locomotor response and increase in absolute dopamine concentration compared to LR rats. The maximum dopamine concentration in the HR group was 23 +/- 2.9 nM, while that in the LR group was only 8.6 +/- 1.1 nM. The maximum in the LR group is comparable to the basal level in the HR group. However, there were no difference in percent change in dopamine following cocaine.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

In vivo calibration of microdialysis probes for exogenous compounds.

Several approaches for calibrating microdialysis probes for exogenous compounds in vivo are described which avoid the error introduced by in vitro calibration. These methods are based on establishing a steady state of the exogenous compound by a continuous (zero-order) iv infusion. The steady-state concentration is estimated by three methods that directly determine the in vivo concentration. The methods are (a) extrapolation of dialysate concentrations at various flow rates to the concentration at zero flow, (b) dialysis with concentrations of analyte added to the perfusion medium above and below the expected concentration to determine the concentration at no net flux across the membrane, and (c) dialysis at a very slow perfusion rate (57 nL/min) where the recovery is expected to be better than 90%. Using these approaches, the recovery for cocaine in the brain was found to be (8.9 +/- 0.68)%, as compared to an in vitro recovery of (5.1 +/- 0.18)% at 24 degrees C and (7.4 +/- 0.18)% at 37 degrees C, at a perfusion rate of 1.2 microL/min through a 0.3- X 2-mm microdialysis probe. The in vivo concentration of cocaine in the rat brain for an intravenous dose of 0.3 mg/kg per min was found to be 17.1 +/- 1.3 microM.

Animals↗
PubMed1992

Anomalous effect of mazindol on dopamine uptake as measured by in vivo voltammetry and microdialysis.

The effect of mazindol on the dopamine (DA) uptake system in the rat striatum was studied by in vivo voltammetry and microdialysis. An increase in the maximal uptake rate was observed by voltammetry 30 min after i.p. administration of 1, 5, 10, 15, and 20 mg/kg doses but not after a dose of 25 mg/kg, while stimulated release was enhanced at all doses. The increased maximal uptake is in contrast to increased levels of extracellular DA observed with microdialysis following mazindol administration. This divergence of action is anomalous in the context of current understanding of the DA uptake system.

Animals↗
PubMed1992

Conditioned locomotor activity but not conditioned place preference following intra-accumbens infusions of cocaine.

In the first experiment, the conditioned place preference (CPP) paradigm was used to examine the rewarding properties of bilateral microinfusions of cocaine HCl into the nucleus accumbens (0, 12.5, 25, 50, or 100 micrograms). No dose of intra-accumbens cocaine induced a significant CPP. However, bilateral intra-accumbens infusions of d-amphetamine sulfate (10 micrograms) or intraperitoneal administration of cocaine HCl (5 or 10 mg/kg) both produced a significant preference for the drug-paired compartment. In the second experiment, the ability of bilateral intra-accumbens infusions of cocaine HCl (50 micrograms) to elicit conditioned locomotor activity (CLA) was examined. During the conditioning trials, intra-accumbens cocaine significantly increased locomotor activity. On the test day, when no drug was administered, the group that had previously received cocaine in the activity chamber showed significantly greater locomotor activity than the vehicle control group. This demonstration of CLA indicates that rats are able to associate the effects of intra-accumbens infusions of cocaine with environmental stimuli; however, these infusions are not rewarding as measured by the CPP paradigm. In addition, these results may indicate important differences between the neural substrates for cocaine and amphetamine reward and reveal a dissociation between CPP and CLA.

Amphetamine↗