Biomedical subjects

J P Huston

Publications and source records attributed to J P Huston.

At least 19 recordsLinked to original sources

PubMed1992

Behavioral and neurochemical indices of barrel cortex-basal ganglia interaction.

Previous experiments from our laboratory have shown a wide variety of time-dependent lateralized changes in behavior and nigrostriatal function following unilateral manipulation of the mystacial vibrissae of rats. The present experiment investigated the effects of unilateral radiofrequency lesion of the cortical vibrissae representation (the barrel fields) in light of these results. We measured lateralized changes in behavior as well as tissue monoamines in neostriatum and substantia nigra, between 1 and 16 days post-lesion. Short-term asymmetries in exploratory behavior (thigmotactic scanning) and neostriatal serotonin metabolism that lasted up to day 6 were seen. In substantia nigra, time-related asymmetries in dopamine concentrations were found with higher ipsilateral values on day 3 and higher contralateral values on day 6. After day 6, the animals had recovered from these acute effects and thereafter, neostriatal dopamine metabolism became asymmetrical. Also during this time, they showed a directional bias in spontaneous and apomorphine-induced turning. Finally, neostriatal serotonin was bilaterally elevated on day 16. These results parallel some of the effects previously seen following unilateral removal of the vibrissae, indicating that the barrel cortex is a critical link in the functional interaction between the vibrissae and basal ganglia.

Animals↗

PubMed1992

The C-terminal fragment of substance P enhances dopamine release in nucleus accumbens but not in neostriatum in freely moving rats.

The in vivo microdialysis technique was used to study the effects of carboxyl or amino terminal sequences of substance P on the extracellular concentrations of dopamine, its metabolites dihydroxyphenylacetic acid and homovanillic acid, as well as on 5-hydroxyindoleacetic acid, in neostriatum and nucleus accumbens of freely moving rats. The i.p. administration of 37 nmol/kg of the substance P C-terminal heptapeptide analog [pGlu5, MePhe8, Sar9]SP5-11 (DiMe-C7) caused an increase in extracellular dopamine concentrations in nucleus accumbens but not in neostriatum. The administration of the equimolar dose of the heptapeptide N-terminal fragment substance P 1-7 (SP1-7) did not have an effect in either structure. No changes were observed in the extracellular concentrations of the metabolites after the administration of either substance. These results are discussed with respect to the reinforcing effects of substance P and its C-terminal sequence, which may be mediated via dopamine release in the nucleus accumbens.

Animals↗

PubMed1992

Unilateral lesion in the tuberomammillary nucleus region: behavioral asymmetries and effects of histamine precursor.

The subnuclei of tuberomammillary nucleus are located in the posterior part of the hypothalamus adjacent to the basolateral surface of the mammillary bodies. The neurons of this nucleus innervate extensive parts of the brain with several transmitters, particularly with histamine. In fact, they represent the only source of histaminergic projections in the brain. The present study deals with the effects of a lesion in this region on behavior. Unilateral electrolytic direct current (DC) lesions in the tuberomammillary nucleus led to an asymmetry in thigmotactic scanning; i.e., at 11 days, but not 1 day postlesion, the rats scanned the walls of an open field more with the vibrissae contralateral to the lesion than with those of the ipsilateral side. Furthermore, they emitted more ipsiversive than contraversive wide angle turns. The behavioral asymmetries are, in general, opposite in direction to those induced by lesion of the neighboring lateral hypothalamus and substantia nigra, indicating that they are specific to the tuberomammillary region destroyed. Application of the histamine precursor histidine led to a compensation of these asymmetries, suggesting that the tuberomammillary's histaminergic efferents are functionally related to the lesion-induced behavioral effects.

Animals↗

PubMed1992

Effects of substance P on extracellular dopamine in neostriatum and nucleus accumbens.

Microdialysis was used to monitor changes in dopamine release in the neostriatum and nucleus accumbens after peripheral administration of substance P in freely moving rats. Substance P in a dose of 50 micrograms/kg produced a steady moderate increase in dopamine levels in the neostriatum, which persisted for at least 5 h. In contrast, a dose of 250 micrograms/kg caused an acute increase in dopamine levels in the nucleus accumbens, which lasted about 2 h. These data suggest that the peripheral administration of substance P can influence dopamine release in mesolimbic and mesostriatal terminals.

3,4-Dihydroxyphenylacetic Acid↗

PubMed1992

Control of turning behavior under apomorphine by sensory input from the face.

It has been shown that peripheral manipulation of sensory input by removal of vibrissae on one side of the rat's face induces turning behavior which is directed towards the contralateral vibrissae-intact side, under the influence of the dopamine receptor agonist apomorphine. In the present experiment, we examined whether rats under apomorphine turn towards the side with more sensory input, or simply away from the manipulated side. Thus, an experimental manipulation was designed to increase sensory input. Sensory stimulation was applied by attaching a clip into the fur on one side of the face. Rats injected with apomorphine in doses of 0.5-5.0 mg/kg (but not with 0.05 mg/kg or vehicle) exhibited turning behavior towards the side of the clip. This sensory stimulation was also found to influence spontaneous behavioral asymmetries. These results show that an imbalance in sensory input is sufficient to produce turning under apomorphine.

Animals↗

PubMed1992

Positively reinforcing effects of the neurokinin substance P in the basal forebrain: mediation by its C-terminal sequence.

The conditioned corral preference paradigm was used to assess reinforcing effects of substance P (SP) and its N- and C-terminal fragments injected unilaterally into the region of the nucleus basalis magnocellularis (NBM) in rats. Behavioral testing was carried out in a circular open field, consisting of 4 quadrants equally preferred by the animals prior to conditioning. A single conditioning trial was performed. Rats received one microinjection (0.5 microliter) of SP (0.74 pmol), of the N-terminal fragment SP (1-7) and the C-terminal fragment analog DiMe-C7 (each at doses of 0.074, 0.74, and 74 pmol), or vehicle (phosphate-buffered saline; PBS). After injection the rats were placed into the open field with the four quadrants being separated by Plexiglas barriers (closed corral). During the test for conditioned corral preference, when provided a choice between the four quadrants, only those rats injected with SP and the equimolar dose of DiMe-C7 (0.74 pmol) spent more time in the treatment corral, indicative of a positively reinforcing action. None of the other doses of DiMe-C7 and of SP(1-7) influenced the preference behavior. For rats injected with 0.74 pmol SP, SP (1-7), and DiMe-C7, a behavioral analysis was performed for the 15 min conditioning trial. SP and DiMe-C7 reduced rearing and grooming behavior, whereas DiMe-C7 and SP(1-7) increased locomotor activity. However, the acute behavioral effects of SP and its fragments were not correlated with the subsequent place preference behavior during the test trial. The results are discussed in the framework of a structure/activity relationship for the positively reinforcing properties of SP in the region of the NBM. Furthermore, neuropathological implications of the present data are considered, since the homologous nucleus basalis of Meynert in man is known to degenerate in Alzheimer's disease, which is characterized behaviorally by a progressive deterioration in associative functioning.

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PubMed1992

Enhanced learning produced by injection of neurokinin substance P into the region of the nucleus basalis magnocellularis: mediation by the N-terminal sequence.

The effect of unilateral injection of the neurokinin substance P (SP) and of certain N- or C-terminal SP-fragments into the region of the nucleus basalis magnocellularis (NBM) on inhibitory avoidance learning was investigated. Rats with chronically implanted cannulae were tested on a one-trial uphill avoidance task. Immediately after the training trial, rats were injected with 0.74 pmol SP or equimolar dosed SP(1-7), DIME-C7, or SP(7-11). Control groups included vehicle-injected rats and a group given an injection of SP(1-7) 5-h after the trial. When tested 24 h later, rats treated with SP or SP(1-7), but not with DIME-C7 or SP(7-11), exhibited longer step-up latencies than vehicle-treated controls. The retention latencies for rats in the SP(1-7) 5-h delay group did not differ from those of vehicle-injected animals, ruling out proactive effects of SP(1-7) on performance. The results show that SP facilitates retention of an inhibitory avoidance response when injected into the NBM. Furthermore, the amino acid sequence that encodes this effect may be located in the N-terminal part of the SP-molecule.

Animals↗

PubMed1992

Behavioral concomitants of regional changes in the brain's biogenic amines after apomorphine and amphetamine.

Behavioral and neurochemical changes were analyzed in rats after systemical injections of the dopamine receptor agonist apomorphine (0.5 mg/kg) or the indirect agonist amphetamine (1.0 mg/kg). As expected, amphetamine led to an increase in locomotion, whereas apomorphine resulted in decreases in locomotion, rearings, and grooming. The analysis of biogenic amines in tissue samples showed that amphetamine decreased 3,4-dihydroxy-phenylacetic acid (DOPAC) levels and DOPAC/dopamine ratios in the neostriatum, and resulted in a lower 5-hydroxyindole-3-acetic acid (5-HIAA)/5-hydroxytryptamine (5-HT) ratio in the ventral mesencephalon. Apomorphine decreased the dopamine metabolites [DOPAC, homovanillic acid (HVA), 3-methoxy-tyramine (3-MT)] and their respective metabolite/transmitter ratios and increased dopamine levels in the neostriatum. Similar decreases in dopamine metabolites or their ratios were found in the ventral mesencephalon, septum, and frontoparietal cortex but not the thalamus. In addition to its effects on dopamine, apomorphine decreased norepinephrine in the ventral neostriatum and 5-HT and 5-HIAA in the cortex. Correlations between behavioral activity and neurochemical metabolism (using the metabolite-transmitter ratios for the latter) revealed relationships between locomotion and serotonergic activity in the thalamus of animals treated with amphetamine. Evidence for a relationship between locomotion or rearings and dopaminergic activity was found in all six brain areas analyzed. Here, the pattern of correlation was dependent on the kind of treatment and the behavioral and neurochemical measures. These results support earlier findings on the neurochemical effects of apomorphine and amphetamine in the neostriatum and ventral mesencephalon, and add new evidence for an action on the septal area, thalamus, and frontoparietal cortex.

Amphetamine↗

PubMed1992

Time-dependent neuroplasticity in mesostriatal projections after unilateral removal of vibrissae in the adult rat: compartment-specific effects on horseradish peroxidase transport and cell size.

In adult rats the mystacial vibrissae were clipped on one side of the snout, and the influence of this sensory deprivation on crossed and uncrossed striatal afferents from the substantia nigra, ventral tegmental area, and retrorubral area was examined with the horseradish peroxidase tract tracing technique. Unilateral removal of vibrissae was found to affect crossed and uncrossed nigrostriatal projections in a time-dependent manner. One to three days after hemivibrissotomy an apparent neuronal asymmetry was found in the crossed nigrostriatal projection arising in the rostral part of the substantia nigra, with more labeled neurons in the projection to the caudate-putamen on the side of vibrissae removal. This asymmetry resulted mainly from an asymmetry in the subset of nigrostriatal neurons reported to project to the striatal matrix ("dorsal cell type"). In contrast, 4-20 days after hemivibrissotomy reversed asymmetries were found in crossed and uncrossed nigrostriatal projections, with more labeled neurons in the projections to the caudate-putamen of the hemisphere opposite to vibrissae removal (the sensory deprived hemisphere). The asymmetry in the uncrossed projection was found throughout the substantia nigra, but was also most substantial in the projection from its rostral part. The asymmetry in the crossed projection was again restricted to the rostral substantia nigra; interestingly, however, it was limited to the subset of neurons reported to terminate in the striosomes ("ventral cell type"). Evidence was also found for time-dependent changes in size of neurons of the crossed nigrostriatal projections, as well as for changes in striatal afferents from the ventral tegmental area. The time course of these apparent changes in strength of mesostriatal projections is similar to the known time course of recovery from behavioral asymmetries induced by hemivibrissotomy, which is suggestive of a functional relationship between neuronal and behavioral changes. Moreover, the finding of a differential influence of hemivibrissotomy on nigrostriatal afferents to striosomes and matrix is indicative of a functional dissociation of these two systems.

Analysis of Variance↗

PubMed1992

Recovery from unilateral 6-hydroxydopamine lesion of substantia nigra promoted by the neurotachykinin substance P 1-11.

Previous work has indicated that the neurotachykinin substance P may have nootropic and neurotrophic effects in vivo and in vitro raising the possibility that this neuropeptide may promote functional recovery from brain damage. This hypothesis was tested using the unilateral 6-hydroxydopamine lesion of the nigrostriatal dopamine system, as there is close anatomical and functional interaction between dopamine and substance P in this system. Rats were unilaterally injected with 6-hydroxydopamine into the substantia nigra, and, starting with the day after the lesion, were treated daily with peripheral injections of substance P (50 micrograms/kg, i.p.). The analysis of open-field behavior showed that, compared with vehicle-treated control lesions, substance P prevented the lesion-induced ipsiversive asymmetry in turning behavior and accelerated recovery from the ipsilateral asymmetry in thigmotactic scanning. The facilitatory effects of substance P were dependent on the degree of the lesion, as they were observed in animals with subtotal neostriatal dopamine depletions but not in those with near-total depletions. These results are discussed, firstly, with regard to the possible mechanisms of substance P on dopaminergic and non-dopaminergic systems, and secondly, with respect to their possible relevance in the study of neurodegenerative diseases.

3,4-Dihydroxyphenylacetic Acid↗

PubMed1991

Changes in the nigrostriatal projection associated with recovery from lesion-induced behavioral asymmetry.

Possible neuronanatomical changes correlated with recovery from lesion-induced behavioral asymmetry were examined. Rats, with 6-OHDA injected into the substantia nigra (SN) on one side, were either assigned to a group with a 48-hour survival period, or one with a 15-day recovery period. Control groups, without a lesion, were also included. All animals were tested for behavioral asymmetry and, at the end of the survival period, had horseradish peroxidase (HRP) deposited in the caudate-putamen (CPU) ipsilateral to the lesion (right or left CPU in the controls). Both substantia nigrae of all animals were examined for HRP-labeled cells. Animals given a 15-day recovery period had more HRP-labeled cells in the SN ipsilateral to the HRP deposition site than those given a 1-day recovery period. Also animals which showed behavioral recovery had more HRP-labeled cells in their ipsilateral SN than either those which showed no recovery or those which were not given time to recover. Thus, our results suggested that behavioral recovery from lesion-induced asymmetry was associated with an increase in HRP uptake and retrograde transport by the remaining nigrostriatal terminals. Animals which recovered showed the expected decrease in ipsiversive, and increase in contraversive turning with time. Unexpectedly, animals which did not recover exhibited an increase in ipsiversive, and a decrease in contraversive turning with time.

Animals↗

PubMed1991

Naloxone blocks conditioned place preference induced by substance P and [pGlu6]-SP(6-11).

The effect of prior treatment with the opioid receptor (opioceptor) antagonist naloxone on conditioned place preference produced by the neurotachykinin substance P (SP) and its C-terminal hexapeptide analog [pGlu6]-SP(6-11) (SPC) was investigated in rats. Place conditioning was assessed using a circular open field partitioned into four quadrants that were equally preferred by the rats prior to drug treatment. On three successive days, rats received an intraperitoneal (i.p.) injection of naloxone-HCl (1 mg/kg) or vehicle 15 min before an i.p. injection of either 37 nmol/kg SP, equimolar dosed SPC or corresponding diluent vehicle. After injection the rats were placed into their assigned treatment corral for 15 min. During the test for conditioned corral preference (CCP), when provided a choice between the four quadrants, rats injected with SP or SPC spent more time in the treatment corral compared to vehicle controls, indicative of a positive reinforcing action of these peptides. The pre-treatment with naloxone blocked the positive reinforcing effects of both SP and SPC; when injected alone, naloxone did not influence the preference behavior. Gross locomotor activity was affected by neither treatment. Thus, the positive reinforcing effects of SP and SPC may be mediated via interactions with the endogenous opioid system(s).

Animals↗

PubMed1991

Relationships between indices of behavioral asymmetries and neurochemical changes following mesencephalic 6-hydroxydopamine injections.

Behavioral and neurochemical changes were investigated in rats that had received one of 3 doses of 6-hydroxydopamine (6-OHDA), injected unilaterally into the ventral mesencephalon. The behavioral analysis comprised that of tight turns (diameter less than 30 cm), wide turns (diameter greater than 55 cm), and locomotor activity. 6-OHDA-injected animals were assigned to 3 different groups according to their degree of asymmetry in tight turns, both in spontaneous behavior and after the dopamine receptor agonist apomorphine (0.05 mg/kg). Thus, 6-OHDA-injected animals showed either (i) no spontaneous ipsiversive asymmetry (group 1), or (ii) an ipsiversive asymmetry, from which they did not recover during the three postoperative weeks of testing and which could not be reversed by apomorphine (group 2), or (iii) an even stronger ipsiversive asymmetry from which they did not recover but which could be reversed by apomorphine (group 3). The analysis of wide turns, which might reflect exploratory behavior of the environment, namely thigmotactic scanning, provided further information, as it indicated an asymmetry even in group 1; however, in contrast to the other groups a contraversive asymmetry was observed. Neurochemically, the three experimental groups were clearly different from each other with respect to the degree of neostriatal dopamine depletion, and the increase in dopamine metabolism in the damaged hemisphere as indicated by increased metabolite/transmitter ratios. The ipsiversive asymmetry in tight turns was negatively correlated with dopamine levels in the damaged neostriatum and positively correlated with the increase in metabolism. Furthermore, indications of changes in neostriatal serotonin activity were found. These results are discussed with respect to the necessity of differential measures of behavioral asymmetry, the role of dopaminergic mechanisms of 6-OHDA-induced deficits and mechanisms of recovery. The asymmetries in tight versus wide turns are suggested to reflect the preponderance of a motor deficit in the former case versus that of sensory neglect in the latter. Thus, the analysis of tight versus wide turns may provide distinctive and sensitive indices related to different functional deficits in animal models of hemiparkinsonism.

Analysis of Variance↗

PubMed1991

Lateralized changes in behavior and striatal dopamine release following unilateral tactile stimulation of the perioral region: a microdialysis study.

Intracranial microdialysis was used to measure dopamine (DA) release in the ventrolateral neostriatum of freely moving rats before and after unilateral tactile stimulation was applied to the orofacial region. Several behavioral parameters which have been linked to changes in nigrostriatal DA transmission (scanning, or snout contact with the walls of the observation chamber, turning and locomotion) were measured as well. Orofacial stimulation was followed by an asymmetrical increase in DA release with concentrations of transmitter higher in the neostriatum ipsilateral to the side of stimulation. Asymmetrical scanning behavior was observed during the time period when DA release was asymmetric, with rats favoring use of the side of the face contralateral to increased DA release. Increases in the DA metabolites DOPAC and HVA were found in the striatum ipsilateral to stimulation, but were delayed 40 min following the increase in DA.

Animals↗

PubMed1991

Asymmetries in thigmotactic scanning: evidence for a role of dopaminergic mechanisms.

In two experiments, the influence of spontaneous asymmetries in thigmotactic scanning was analyzed on spontaneous and drug-induced behavior in the rat. The side of the face with which an animal performed more scanning in a baseline test was defined as the dominant vibrissae side. In experiment 1, repeated testing of either spontaneous thigmotactic scanning, or scanning after apomorphine or amphetamine, yielded no evidence that rats would preferably use one side of the face for scanning, when re-exposed to the same environment. However, an asymmetry in turning was observed both under apomorphine and amphetamine, that is, turning away from the dominant vibrissae side. In experiment 2, an influence of spontaneous asymmetries in scanning was found on behavioral asymmetries induced by unilateral vibrissae removal. Only animals, in which the vibrissae of the non-dominant side had been removed, showed more scanning with the intact vibrissae side, both undrugged and after apomorphine. Turning under apomorphine was more pronounced in animals in which the vibrissae on the dominant side had been removed. These animals showed an asymmetry in turning towards the intact vibrissae side. Furthermore, in both experiments we found evidence for left/right differences in turning or scanning. The results are discussed with respect to possible endogenous substrates of asymmetry, such as within the mesostriatal dopamine system.

Amphetamine↗

PubMed1991

Trigeminal-basal ganglia interaction: control of sensory-motor gating and positive reinforcement.

Functional interactions between the basal ganglia and the perioral area were analyzed by means of electrical brain stimulation in the rat. The first experiment showed that unilateral stimulation of the substantia nigra sensitized the contralateral perioral area for a biting reflex upon its tactile stimulation. This biting reflex consists of lip withdrawal, orienting towards and biting into the stimulus source. The same sites in the substantia nigra also produced electrical self-stimulation using bar-pressing as the operant. A positive correlation was found between threshold currents for biting and for self-stimulation. However, the current levels necessary for reinforcement were considerably higher than those to facilitate the biting reflex. In the second experiment, it was found that manipulation of the perioral area by unilateral vibrissae removal reduced the rate of electrical self-stimulation in the substantia nigra. This effect was lateralized, depended on time after vibrissae removal, and could be reversed by systemic injections of the dopamine receptor agonist apomorphine. These results, which provide evidence for a reciprocal interaction between the basal ganglia and the perioral area, are discussed with respect to mechanisms of sensory-motor gating, motivation and reinforcement.

Animals↗

PubMed1990

The interhemispheric projection from the substantia nigra to the caudate-putamen as depicted by the anterograde transport of [3H]leucine.

The organization of the interhemispheric projections from the substantia nigra to the caudate-putamen was examined after [3H]leucine had been injected into the substantia nigra on one side. There was not a strict correspondence between the regions of termination of the crossed and homolateral nigrostriatal projections. Although the leucine predominantly labeled the lateral parts of the ipsilateral caudate-putamen, terminal labeling was also found in the medial and lateral parts of the contralateral caudate-putamen. The crossed nigrostriatal projection terminated in discrete areas of variable size in the contralateral caudate-putamen. The patterns made by the silver granules in the caudate-putamen contralateral to the [3H]leucine injection appeared to be heterogeneous.

Animals↗

PubMed1990

Reinforcing effects of peripherally administered substance P and its C-terminal sequence pGlu6-SP6-11 in the rat.

Reinforcing effects of intraperitoneally (IP) administered substance P (SP1-11), its amino-terminal fragment SP1-7 (SPN) and an analog of the carboxy terminus (pGlu6-SP6-11: SPC) were studied in rats. Two conditioned place preference paradigms were used. After three pairings of the drug with a certain environment the effect of the treatment was evaluated in the drug-free state during a test trial. The reinforcing effects of SP (37 nmol) and the equimolar dose of SPC were expressed by a significant increase in the amount of time the animals spent in the treatment environment. Other doses of SP (3.7 and 185 nmol) and SPC (7.4 and 185 nmol) and none of the doses of SPN (37, 185, 370 nmol) influenced the place preference behavior of the rats. The reinforcing effects of SP parallel the known facilitating effects of peripherally administered SP on memory. The amino acids that encode the reinforcing effects of SP may lie within the C-terminal sequence of the SP molecule.

Animals↗