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C Szostak

Publications and source records attributed to C Szostak.

13 recordsLinked to original sources
PubMed1989

Neurochemical correlates of conditioned circling within localized regions of the striatum.

Two experiments were conducted to determine the effects of conditioned circling on the concentrations of dopamine (DA), 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) within discrete regions of the striatum (STR). The first study assessed the inherent regional distributions of these compounds with respect to the three primary axes: anterior-posterior, dorsal-ventral and medial-lateral. Concentrations of DA, DOPAC and HVA and the ratios of each metabolite to DA were found to vary across each dimension. However, the topographical distribution of each compound was unique. The results of the first experiment confirm that the STR is not a homogeneous structure. It is possible that the regional variations in dopamine metabolism underly the diverse functions which the STR is thought to modulate. The second experiment determined whether specific regions of the STR were differentially involved in the mediation of conditioned circling. DA metabolism, as estimated by metabolite concentrations and metabolite to DA ratios, was bilaterally increased within the anterior dorsomedial and dorsolateral STR, relative to noncircling, water-deprived controls. DOPAC and the corresponding ratio were enhanced selectively within the dorsomedial region, whereas HVA and its ratio to DA were increased preferentially within the dorsolateral STR. The ratio of DOPAC to DA was also enhanced within the anterior ventromedial STR. No other significant neurochemical effects were detected. These results support the hypothesis that the dorsal STR critically subserves circling. Moreover, it is possible that the medial and lateral regions of the dorsal STR are differentially involved in circling. These results also confirm previous reports of bilateral augmentation of striatal DA metabolism in association with high rates of conditioned circling.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1989

Influence of inherent directional biases on neurochemical consequences of conditioned circling.

High rates of conditioned circling have been associated with a bilateral increase in striatal (STR) dopamine (DA) metabolism in rats. Experiments 1 and 2 examined the extent to which inherent directional biases, which are critical in determining the magnitude and direction of drug-induced circling, would influence the acquisition and performance of conditioned circling. No behavioral effects were evident. However, a symmetrical bilateral enhancement in DA metabolism was observed in the STR irrespective of directional biases. These results provide further evidence for the bilateral involvement of the mesotelencephalic DA projection in conditioned circling. Although conditioned circling could be established and maintained by reinforcing the response with food (Experiment 3), food itself influenced DA metabolism and therefore precluded the detection of changes in DA metabolism specific to the circling response. Specifically, DA metabolism was augmented to a similar extent in animals given noncontingently presented food.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1988

Conditioned circling in rats: bilateral involvement of the mesotelencephalic dopamine system demonstrated following unilateral 6-hydroxydopamine lesions.

High rates of conditioned circling have previously been associated with a bilateral augmentation of striatal dopamine metabolism. These results suggest that both striata subserve this response. The present experiment further assessed this possibility by determining the effects of unilateral 6-hydroxydopamine lesions of the mesotelencephalic dopamine system on conditioned circling. Rats were initially trained to circle in their preferred direction for water reinforcement. Upon establishment of this response, they received unilateral lesions at the level of the lateral hypothalamus either contralateral or ipsilateral to the reinforced direction of circling. Reinforced responding was virtually abolished in rats with contralateral lesions. In contrast, rats lesioned ipsilateral to the direction of reinforced circling exhibited only a 50% decrease in rate of reinforced responding. Non-reinforced responding was increased only in rats with contralaterally placed lesions. Following 5 postoperative test sessions, the experimental contingencies were reversed. 'Ipsilaterally lesioned' rats were now required to circle away from their lesion whereas 'contralaterally lesioned' rats had to turn towards their lesion. The 'Contralateral' group acquired the reversal, such that reinforced responding occurred more frequently than non-reinforced responding. However, reinforced rates of responding did not reach preoperative rates. Conversely, 'ipsilaterally lesioned' rats could not learn to turn contraversively and now made more non-reinforced than reinforced responses. These findings suggest that conditioned circling is mediated by a bilateral involvement of the mesotelencephalic dopaminergic systems. However, the specific role of each side appears to be dependent upon its relationship with the direction of circling emitted.

Animals↗
PubMed1987

Intravenous self-administration of the short-acting benzodiazepine midazolam in the rat.

Intravenous self-administration of the short-acting benzodiazepine midazolam was assessed in rats under conditions of unlimited access to the drug (24 hr/day). Evaluation of the temporal pattern of responding within a session revealed that maximal responding occurred during the dark phase of the 12 hr light/dark cycle. Upon attaining stable rates of responding for midazolam, the rats were tested under extinction conditions (saline). Responding progressively decreased with repeated extinction sessions. Over the course of subsequent reacquisition sessions responding increased, such that asymptotic levels of responding were similar to, or greater than, the rates obtained during the initial acquisition phase. In addition, the total number of sessions required to approach asymptote were fewer than during the initial acquisition phase. Thus, rats given continuous access to midazolam exhibited reliable and stable rates of intravenous self-administration of this short-acting benzodiazepine.

Animals↗
PubMed1986

6-Hydroxydopamine lesions of the medial prefrontal cortex fail to influence intravenous self-administration of cocaine.

It has been suggested that the initiation and maintenance of cocaine self-administration (SA) is critically dependent on the dopaminergic (DA) projection to the medial prefrontal cortex (mPFC). Evidence for this hypothesis has been obtained from intracranial SA of cocaine, but a role of the mPFC in IV cocaine SA has not been established. The present experiment investigated the effect of destruction of DA-containing terminals in the mPFC on the rate and pattern of IV cocaine SA. Rats were trained to self-administer cocaine during daily 3-h sessions. After stable response patterns were obtained, the rats received either bilateral injections of 6-hydroxydopamine (6-OHDA) into the mPFC, or sham operations. The lesions did not affect either the rate or pattern of IV cocaine SA, despite producing substantial DA depletions in the mPFC. Thus, the mPFC does not appear to be a critical substrate for the maintenance of IV cocaine SA. The 6-OHDA lesions of the mPFC resulted in an apparent increase in DA turnover in both the striatum and the nucleus accumbens, suggesting that DA terminals in the mPFC may have an inhibitory influence on the activity of subcortical DA projections.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1986

Dopaminergic and serotonergic correlates of stimulation-induced circling.

Rotation induced by electrical stimulation of the medial forebrain bundle at the level of the lateral hypothalamus was associated with increases in dopamine (DA), 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) in the striatum ipsilateral to the site of stimulation (i.e. contralateral to direction of turning). The concentrations of DA, DOPAC and HVA within the nucleus accumbens (NAS) were not altered. In the olfactory tubercle (OT), concentrations of DA and both metabolites were, in general, elevated ipsilateral to the electrode. However, relative to non-stimulated controls, HVA concentrations were increased bilaterally in rats exhibiting circling. Stimulation-induced circling also resulted in a bilateral enhancement of striatal serotonin (5-HT) metabolism as indicated by elevated 5-hydroxyindoleacetic acid: 5-HT ratios. No changes in 5-HT metabolism were observed in the NAS. The utilization of 5-HT was elevated in the OT ipsilateral to the electrode in rats that exhibited stimulation-induced rotation. While most subjects that exhibited contraversive rotation in response to the stimulation demonstrated enhanced DA activity, the neurochemical changes were not observed in all subjects. As such, it is concluded that while stimulation of the mesotelencephalic DA system can be associated with stimulation-induced rotation it is not necessary for its elicitation.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1986

Bilateral augmentation of dopaminergic and serotonergic activity in the striatum and nucleus accumbens induced by conditioned circling.

The involvement of dopaminergic (DA) and serotonergic (5-HT) systems in circling was assessed by determining the neurochemical correlates of circling induced and maintained by two different schedules of water reinforcement. The conditioned circling paradigm was employed in an attempt to replicate reports that levels of DA and 3,4-dihydroxyphenylacetic acid (DOPAC) were increased in the striatum and nucleus accumbens septi (NAS) contralateral to the direction of circling. Rats trained to circle using a continuous schedule of reinforcement did not exhibit any changes in concentrations of DA, DOPAC, or homovanillic acid (HVA). Bilateral increases in 5-HT concentrations were observed in the striatum. Use of an intermittent schedule of reinforcement (FR-2) produced higher rates of circling. In rats maintained on the FR-2 schedule, no changes in DA or its metabolites were observed in the striatum. The ratio of HVA to DA was, however, increased bilaterally, suggesting a bilateral augmentation of DA utilization. Concentrations of DA were lower in the NAS contralateral to direction of turning. While NAS levels of HVA were elevated bilaterally when compared to non-circling controls, HVA was lower in the NAS contralateral to the direction of circling. DA utilization, as estimated by HVA: DA ratios, was increased bilaterally in the NAS. None of the measures of DA activity within the olfactory tubercle (OT) were influenced by circling. Turnover of 5-HT, as estimated by the ratio of 5-HT to 5-hydroxyindoleacetic acid (5-HIAA), was increased bilaterally in the striatum, NAS, and OT.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1985

Stimulus perseveration in a water maze following exposure to controllable and uncontrollable shock.

When placed in a water-filled maze, mice display a pronounced preference for the illuminated over the nonilluminated arm of the maze. Exposure to inescapable shock increased the time spent in the illuminated arm of the maze, and decreased the frequency of entries into the nonilluminated arm. When animals that had received shock entered the nonilluminated arm they exhibited more activity per second than nonstressed animals. Controllability over the stressor enhanced the preference for the illuminated arm; however, the contribution of this variable was dependent on the number of shock trials mice received. Following 180 escapable or inescapable shock presentations the preference for the illuminated arm was enhanced. The propensity to approach the illuminated arm declined following a greater number (360) of escapable shock trials, while the preference for the illuminated arm did not decline in mice that received inescapable shock. Both escapable and inescapable shock were also found to produce a transient disruption of discrimination performance in a task where animals were required to emit a contraprepared response (swim to dark), whereas these treatments were without effect on performance of the highly prepared response of approaching the illuminated arm. It is provisionally suggested that enhancement of the perseveration represents an innate response to stressful stimuli, but as animals learn mastery over the response contingencies, the persistence in adopting such a response strategy wanes. Moreover, despite the differential effects of escapable and inescapable shock on the perseverative tendency, discrimination accuracy may not be differentially affected by these treatments in a task where acquisition progresses quickly and where explicit cues are associated with the correct and incorrect arms of the maze.

Animals↗
PubMed1983

Failure to replicate the dorsal bundle extinction effect: telencephalic norepinephrine depletion does not reliably increase resistance to extinction but does augment gustatory neophobia.

Depletion of telencephalic noradrenaline (Ne), caused by lesion of the dorsal tegmental bundle, has been reported to increase persistence of non-reinforced responding in various operant tasks. This has been referred to as the dorsal bundle extinction effect (DBEE). In an effort to reproduce this effect, rats receiving 6-hydroxydopamine lesions of the dorsal Ne bundle (DB-6-OHDA) were compared to controls during extinction of a continuous food rewarded (CRF) lever-press response. While the lesion group showed an increase in responding during initial extinction, no significant difference in resistance to extinction using a 2-min non-response criterion was obtained. Moreover, no differences in reinforced response rates were observed with CRF, fixed ratio (FR-15, FR-30, FR-60) or variable interval (VI-30, VI-60, VI-120 s) schedules of reinforcement. In order to test the hypothesis that the DBEE is dependent on time of behavioral testing after surgery, subsequent experiments were performed where rats began CRF operant training 5, 17, 31 or 110 days post-lesion. No differences in resistance to extinction were observed between lesion and control rats at any post-lesion interval. Neonatal treatment with 6-OHDA which permanently lesions forebrain Ne terminals also failed to prolong extinction. Finally, when both DB-6-OHDA and neonatal rats were given a choice between water and saccharin the lesioned animals exhibited a neophobic reaction whereby they drank significantly less saccharin. We conclude that while the DBEE is not a reliably reproducible phenomenon other effects of forebrain Ne lesions, such as neophobia, appear to be robust.

Afferent Pathways↗
PubMed1983

Failure of pimozide to disrupt the acquisition of light-dark and spatial discrimination problems.

The effects of pimozide, a dopamine (DA) receptor blocker, on associative learning was examined using two appetitively motivated choice paradigms. In Experiment I, low to moderate doses of pimozide (0.125, 0.25 mg/kg) were not found to disrupt the acquisition of a two bar simultaneous discrimination task. However, with continued testing, progressive deficits in response accuracy were observed in rats pretreated with 0.25 mg/kg pimozide. When subsequently tested drug-free these animals demonstrated a rapid and marked improvement in performance. Experiment II used a spatial discrimination task (T-maze) requiring a natural response (running) with minimal response demands (short stem and arms). Rats pretreated with 0.25, 0.50, and 1.0 mg/kg pimozide showed comparable levels of acquisition and maintained discriminated performance relative to vehicle controls. Similar results were obtained when the reinforced (S+) and nonreinforced (S-) stimuli were reversed. Moreover, animals receiving 2.0 mg/kg pimozide and not rendered cataleptic also demonstrated acquisition of both the initial discrimination and its reversal. It was concluded that rats pretreated with pimozide are able to acquire the significance of environmental stimuli and direct their responding accordingly if they are motorically capable of emitting the required response.

Animals↗
PubMed1982

Failure to obtain functional equivalence between dopamine receptor blockade and extinction: evidence supporting a sensory-motor conditioning hypothesis.

The effects of pimozide were tested in a discrete trial paradigm. Following 8 days of continuous reinforcement training with a retractable bar, subjects were divided into 3 groups: Vehicle-Extinction; Pimozide-Extinction and Pimozide-Reinforcement. Pimozide rats received 1 mg/kg of drug 4 hours prior to test. On each of 3 test days reinforcement continued to be delivered on a continuous reinforcement schedule for the Pimozide-Reinforcement Group whereas it was no longer delivered for the other two groups. Each test day was separated by 4 drug-free days. The Pimozide-Reinforcement Group showed the least response suppression, followed by the Vehicle-Extinction and Pimozide-Extinction Groups. These results do not support the anhedonic hypothesis that dopamine containing neurons mediate reward processes and were interpreted within a sensory-motor conditioning framework.

Animals↗
PubMed1981

Use of a fixed consecutive number schedule of reinforcement to investigate the effects of pimozide on behavior controlled by internal and external stimuli.

The effects of the neuroleptic pimozide, a specific dopamine receptor blocker, on behavior maintained under different degrees of stimulus control was examined by using a fixed consecutive number (FCN) schedule of reinforcement with pigeons. This schedule requires that at least eight consecutive responses be made on one key (work key) before a response on a second key (reinforcement key) will be reinforced. For half the birds no change in external stimuli accompanied the eight response (FCN-8) while for the other half the color of the work key changed from white to red after the eight peck (FCN-SD). Both schedules resulted in equal rates of baseline responding. Four doses of pimozide (vehicle, 0.1, 0.3, 0.5 mg/kg) were administered in a Latin Square sequence after baseline responding was stable. Similar pimozide-induced decreases in responding were observed in both conditions. However, pimozide selectively altered response patterns under the FCN-8 condition. The failure of the FCN-SD procedure to display a similar effect demonstrated that the use of salient exteroceptive stimuli can modulate behavioral deficits induced by pimozide. This conclusion has important implications for theories hypothesizing that dopamine subserves reward processes.

Animals↗