Dopamine Utilization Research Articles

Alterations in light-evoked dopamine metabolism in dystrophic retinas of mutant rds mice

In dystrophic retinas of rds mice, which are devoid of photoreceptor outer segments, high steady state levels of dopamine were found in dark and light periods. These levels were similar to those observed in normal, BALB/c mouse retinas. Major differences were determined, however, between dopamine turnover in normal and dystrophic retinas. While substantial light-evoked elevation of dopamine synthesis and utilization was observed in normal retinas, dopamine synthesis and metabolism in rds retinas was very low and response to light was depressed. Retinal dopamine metabolism was already depressed in 2 week old rds mice, prior to the onset of photoreceptor cell death, relative to that in age-matched BALB/c mice. At 1 month of age, robust light/dark differences in retinal dopamine metabolism were observed in BALB/c mice, while no significant effect of light was seen in rds mice. The limited ability of the dopaminergic system in rds retinas to respond to light may be due to the absence of normal outer segments. Interestingly, in old rds retinas, although most photoreceptor cells had degenerated, a small but significant light-evoked increase in dopamine metabolism was measured. The presence of relatively high steady state levels of dopamine in rds retinas, despite the reduced dopamine synthetic activity, is maintained by a compensatory reduction in dopamine utilization. Thus, although a considerable amount of dopamine is present in the rds retina, it might not be available to exert its biological functions.

Cytokine-specific central monoamine alterations induced by interleukin-1, -2 and -6

Cytokine-specific alterations of monoamine activity were evident in the hypothalamus, hippocampus and prefrontal cortex 2 h following peripheral administration of recombinant interleukin (IL)-1β, IL-2 and IL-6 (200 ng, i.p.) in male, BALB/c mice. IL-1 induced the broadest range of neurochemical changes, affecting central norepinephrine (NE), serotonin (5-HT) and dopamine (DA) activity. In particular, IL-1 enhanced NE turnover in the hypothalamus and hippocampus, 5-HT turnover in the hippocampus and prefrontal cortex (owing to increased utilization and reduced content of the transmitters in these brain regions), and enhanced DA utilization in the prefrontal cortex. IL-6 increased 5-HT and DA activity in the hippocampus and prefrontal cortex in a manner similar to IL-1, but failed to affect central NE activity. Moreover, IL-2 increased hypothalamic NE turnover (reflecting a profound increase in NE utilization) and enhanced DA turnover in the prefrontal cortex, but did not influence central 5-HT activity. Hence, these cytokines differentially altered neurochemical activity in brain regions that mediate neuroimmune interactions and that are influenced by physical and psychological stressors. In addition to the neurochemical changes, plasma corticosterone concentrations were profoundly enhanced in IL-1-treated animals, but not significantly altered by IL-2 or IL-6 treatment. The IL-1-induced corticosterone elevations did not significantly correlate with alterations of hypothalamic NE activity.

Adrenal response to long-term hypoxia is still increased after carotid body denervation in rat.

This study investigated the effects of long-term normobaric hypoxia (10% O2 in N2 for 2, 7, 14, and 28 days) on the metabolism of catecholamines in rat adrenals and the role of the carotid body chemoreceptors in the adrenal response. The content and utilization of dopamine were significantly increased from the 7th day of hypoxia and remained enhanced thereafter. The content of norepinephrine and epinephrine decreased after 2 days of hypoxia and increased thereafter; after 28 days of hypoxia the norepinephrine amounts remained enhanced but the epinephrine levels were no longer significantly increased. In vivo tyrosine hydroxylation increased after 7 days of hypoxia. Bilateral transection of the carotid sinus nerve 1 wk before hypoxia failed to abolish the increase in the content and utilization of dopamine after 7, 14, or 21 days of hypoxic exposure. These results indicate that long-term normobaric hypoxia elicits a long-lasting increase in the metabolism of catecholamines in adrenals, especially as assessed by dopamine measurement, and that this response does not involve a carotid body chemoreflex pathway.

Carotid body dopamine response to acute hypoxia in developing rabbits.

Dopamine (DA) is present at high concentration in the carotid body (CB) of different mammalian species, and may influence the functional properties of chemosensory cells, particularly their response to hypoxia. Long-term exposure to hypoxia produces a significant increase in DA synthesis and utilization; while short-term exposure to low PO2 induces a decrease in carotid body DA content indicating an increased release from glomus cells. This release has been shown to be proportional to both the level of PO2 and the carotid chemosensory activity (see for review Fidone et al. (1990)). In adult as in newborn animals in vivo and in vitro, studies have shown that dopamine may induce an inhibition and/or an excitation of carotid chemoreceptors activity (Fidone et al., 1990; Marchal et al., 1992; Zapata, 1975). The excitatory effect is predominant in young animals especially in hypoxia (Marchal et al., 1992). The variation in DA effect may be due to developmental changes in either chemoreceptor response to DA or in carotid body dopamine response to hypoxia. The aim of this study was to characterize the carotid body dopamine content and release in response to acute hypoxia in developing rabbits.

PEC-60, a Novel Regulatory Peptide Reduces Cyclic AMP Formation in Rat Caudate Nucleus

PEC-60, a sixty-residue novel regulatory peptide with N-terminal glutamic acid and C-terminal cysteine is abundant in intestinal tissue. PEC-60-like immunoreactivity is found in catecholamine neurons and intracerebroventricular injections of PEC-60 reduce dopamine utilization within the caudate nucleus indicating a possible role of this peptide in the central nervous system. We have investigated the effect of PEC-60 on cAMP formation in membrane preparations from rat caudate nucleus. We have found that PEC-60 significantly and dose-dependently reduces basal and forskolin stimulated cAMP production. The results demonstrate for the first time the interaction of PEC-60 with specific binding sites that regulate adenylate cyclase in inhibitory fashion in rat caudate nucleus.

Stress activation of mesocorticolimbic dopamine neurons: Effects of a glycine/NMDA receptor antagonist

Restraint of brief duration causes a metabolic activation of mesocortical and some mesolimbic dopaminergic systems with little effect on the nigrostriatal system. We have examined the ability of an antagonist of the allosteric glycine site of the N-methyl-D-aspartate receptor complex to block the stress-induced response in dopamine utilization. Thirty minutes of restraint stress elevated dopamine metabolism, as measured by the ratio between 3,4-dihydroxyphenylacetic acid (DOPAC) and dopamine, in both the medial prefrontal cortex and nucleus accumbens. An antagonist for the glycine/N-methyl-D -aspartate receptor complex, 1-hydroxy-3-aminopyrrolidone-2 ((+)-HA-966), given systemically or injected into the ventral tegmental area, prevents the stress-induced increase in dopamine metabolism in the prefrontal cortex without altering the response in the nucleus accumbens. Similarly, systemic administration of the non-competitive antagonist for the N-methyl-D-aspartate receptor, dizocilpine ((+)-MK-801), blocked the stress-induced rise in dopamine metabolism in the medial prefrontal cortex but not the nucleus accumbens. The negative enantiomer of HA-966 did not produce a selective antagonism of the stress-induced dopamine metabolism in the medial prefrontal cortex. These results support previous work which suggest the mesocortical and mesoaccumbens dopamine neurons respond to excitatory input through different glutamate receptor mechanisms. Additionally, the specific blockade of the stress-induced change in dopamine metabolism in the medial prefrontal cortex by a glycine antagonist implies a role for such an antagonist in treatment of disease states which may involve disruptions of N-methyl-D-aspartate receptor function.

Modifications of striatal D2 dopaminergic postsynaptic sensitivity during development of morphine tolerance-dependence in mice

Alterations in the activity of striatal dopaminergic neurons have been implicated in the development of morphine tolerance-dependence in rodents. To further explore this possibility, we examined the activity of these neurons in mice exposed to morphine during 4 days (addiction group) and subsequently treated with naloxone (withdrawal group). The efficiency of opiate treatment was assessed behaviorally. Striatal dopaminergic activity was evaluated by measuring: a) the ratio between the amounts of L-3,4-dihydroxyphenylacetic acid (DOPAC), the main intraneuronal metabolite of dopamine (DA), and the neurotransmitter itself, as an index of presynaptic activity; and b) the number and affinity of D1 and D2 dopaminergic receptors, as well as the amount of their coupled second messenger, cyclic adenosine monophosphate (cAMP), as postsynaptic parameters. Spontaneous motor activity was decreased in chronically morphine-exposed mice. In these animals, the number of striatal D2 receptors also decreased, with no changes in their affinity, whereas the number and affinity of D1 receptors remained uncharged. This hyposensitivity of D2 receptors was paralleled by an increase in the amount of cAMP with a good statistical correlation between both parameters. Treatment with naloxone of morphine-exposed mice resulted in the typical jumping behavior indicative of opiate withdrawal. The differences in D2 receptors between placebo- and morphine-exposed mice disappeared after naloxone-induced opiate withdrawal, although this effect was due more to the inhibitory effect of naloxone on the density of these receptors in placebo-exposed mice rather than to a stimulatory effect in morphine-addicted mice. The morphine-induced increase in cAMP content also disappeared after naloxone treatment. No significant changes occured in the presynaptic activity in both states, as reflected by the absence of changes in the DOPAC/DA ratio. However, DA storage decreased after the induction of opiate withdrawal, which could be related to a repeated DA utilization during the naloxone-induced jumping behavior in morphine-addicted mice. In summary, our results provide neurochemical evidence of changes in striatal dopaminergic neurotransmission concomitant to the typical motor alterations produced during morohine tolerance-dependence. These changes were mainly produced at the postsynaptic level, by decreasing the number of D2 receptors and increasing the cAMP production, during the morphine addiction. These differences disappeared after the naloxone-induced morphine withdrawal, likely by an inhibitory effect of naloxone on D2 receptors in placebo-exposed mice. Moreover, a presynaptic effect could be suspected during the opiate withdrawal in view of the decrease in DA content observed in naloxone-treated morphine-exposed mice.

Narcolepsy: pathogenesis and nursing care.

Narcolepsy is a chronic, incurable disorder affecting at least a quarter of a million Americans. It is characterized by a tetrad of symptoms, which include excessive daytime sleepiness, cataplexy, sleep paralysis and hypnogogic hallucinations. Individuals may experience severe negative psychosocial consequences associated with these symptoms. The neuropathology of narcolepsy is largely unknown. Current work implicates decreased production or utilization of norepinephrine, dopamine and serotonin in the brain, and excessively numerous or hypersensitive cholinergic receptors in the brain. Medical management includes the use of separate drug therapies to control sleep attacks and cataplectic episodes. Nursing management requires comprehensive assessment of the interplay between the patient and environment and assistance with long-term coping.

The locus coeruleus and dopaminergic function in rat brain: Implications to Parkinsonism

Clinical and experimental evidence suggests that degeneration of the locus coeruleus (LC) may be responsible for certain symptoms of Parkinson's disease (PD). We have, therefore, studied the effects of LC lesion on dopamine (DA) metabolism in the rat striatum. Unilateral depletion of norepinephrine (NE) was obtained by stereotaxic injection of 6-hydroxydopamine (6-OHDA) into the dorsal NE bundle (DNEB). Rats were sacrificed 1 or 3 weeks after lesioning. 6-OHDA induced approximately 50% depletion of NE in the ipsilateral hippocampus at 1 week postinjection and over 75% depletion after 3 weeks. DNEB lesions had no effect on DA or DOPAC levels in the ipsi- or contralateral striatum at either time point. Lesions also failed to affect DA synthesis or utilization in either striatum. The metabolism of exogenous levodopa in the striatum was also unaffected. It is suggested that any possible effect of the LC on DA transmission in the striatum is not mediated by the DNEB.

Early postnatal clonidine treatment results in altered regional catecholamine utilisation in adult rat brain.

Clonidine is a clinically used antihypertensive which has been suggested to produce physiological changes in children after exposure in utero. The aim of our study was to test the hypothesis that chronic exposure of the developing brain to an alpha 2-adrenergic agonist like clonidine would influence the adult neurochemical setting of central monoamine neurotransmitter systems. Male rat pups were treated from postnatal day 8 to 21 twice daily with saline or with 0.1 mg/kg clonidine. After the last injection on day 21, brain regional catecholamine utilisation was determined using synthesis inhibition with alpha-methyl-p-tyrosine in a subgroup of the pups. The expected decrease in noradrenaline utilisation after clonidine was observed, although statistical significance was not reached in a number of brain regions. Dopamine utilisation was not affected. The other pups were left to reach young adulthood and catecholamine utilisation was measured on day 90. Noradrenaline utilisation on day 90 was significantly decreased in two regions: the medulla-pons and the mesolimbic (dopamine projection) areas. Dopamine utilisation was decreased in the hypothalamus and increased in the amygdala and the cerebellum. These adult neurochemical alterations corroborate previous findings of adult behavioural, physiological and central biochemical alterations in rats exposed to clonidine in early postnatal life.

Supersensitivity of spinal dopaminergic receptors in rat after chronic haloperidol

In order to examine the effect of chronic neuroleptics on spinal dopaminergic system, rats were treated with haloperidol (0.5 mg/kg IP) for 21 days and the monosynaptic mass reflex (MMR) as well as dopamine (DA) metabolism were investigated. MMR, recorded from ventral root L6 following supramaximal stimulation to ipsilateral dorsal root L6 in spinalized rats, were found to be unaffected following chronic haloperidol treatment when compared to control. Apomorphine (0.1 mg/kg IV) caused 10–20% depression of MMR in control animals which was augmented to 40–50% in chronically haloperidol-treated animals suggesting an upregulation of DA receptors in the spinal cord. DA content of lumbar region of the spinal cord was unaffected whereas its major metabolite, homovanillic acid, was significantly reduced in chronic haloperidol-treated animals. This decreased utilization of DA may compensate the upregulation of DA receptors to maintain the physiological homeostasis of the spinal dopaminergic system.

The regulation of subcortical dopamine systems by the prefrontal cortex: interactions of central dopamine systems and the pathogenesis of schizophrenia.

A recent hypothesis of the pathogenesis of schizophrenia posits a developmentally-specific dysfunction of the dopaminergic innervation of the prefrontal cortex (PFC; Weinberger, 1987; Berman and Weinberger, 1990). It has been difficult to reconcile this hypothesis with the observation that all clinically effective antipsychotic drugs used for the treatment of schizophrenia block dopamine D2 receptors (see Deutch et al., 1991a). A resolution between the suggestion of functional dopamine (DA) "depletion" in the PFC and enhanced subcortical DA function was offered by studies of Carter, Pycock, and associates (Carter and Pycock, 1980; Pycock et al., 1980a, b). These investigators reported that depletion of DA in the rat PFC enhanced DA utilization in subcortical sites such as the nucleus accumbens septi (NAS) and striatum. Thus, a functional deficit in DA neurotransmission in the PFC would increase subcortical DA turnover, and the D2 receptor blockade induced by antipsychotic drugs would counteract the increase in dopaminergic tone in subcortical sites. This hypothesis has been particularly influential because it incorporates both an explanation for negative symptoms, which are thought to reflect cortical dysfunction (a derangement in DA transmission in the PFC), and the efficacy of antipsychotic drugs in the treatment of positive symptoms (arising from increases in subcortical DA tone). As attractive as this hypothesis has been, the physiological underpinnings that subserve such system interactions have remained elusive. Pycock, Carter, and colleagues (Carter and Pycock, 1980; Pycock et al., 1980a, b) reported that 6-hydroxydopamine (6-OHDA) lesions of the PFC increase DA levels and DA turnover in the striatum; certain aspects of their findings have been confirmed (Martin-Iversen et al., 1986; Leccese and Lyness, 1987; Haroutounian et al., 1988). However, other groups have been unable to confirm either the biochemical or behavioral findings of Pycock and associates (Joyce et al., 1983; Oades et al., 1986; Deutch et al., 1990). Moreover, Pycock and colleagues did not observe consistent effects of PFC DA deafferentation on various indices of subcortical DA function (Carter and Pycock, 1980; Pycock et al., 1980a, b). In light of the importance that such DA system interactions may have in the pathogenesis of schizophrenia, we have reinvestigated the effects of cortical DA lesions on subcortical DA function.

Pharmacological characterization of dopamine systems in the nucleus accumbens core and shell

Recent anatomical data suggest that the nucleus accumbens can be parcellated into a core region, related to the caudate-putamen, and a shell region, associated with the limbic system. We have used pharmacological methods to characterize the dopamine innervations of the nucleus accumbens core and shell in the rat. Concentrations of both dopamine and serotonin were significantly greater in the nucleus accumbens shell than the nucleus accumbens core. Metabolite: amine ratios suggested that both dopamine and serotonin utilization are greater in the core. However, dopamine turnover (as determined by measuring the rate of decline of dopamine after α-methyl- p-tyrosine treatment) was not significantly different in the two accumbal sectors. Dopamine concentrations in the two nucleus accumbens sectors were decreased to an equivalent degree at both 4 and 18 h after reserpine administration. In contrast, serotonin concentrations were decreased to a significantly greater degree in the nucleus accumbens core than nucleus accumbens shell at 4 h, but not 18 h, after reserpine administration. Administration of haloperidol increased dopamine utilization in both nucleus accumbens sectors, but augmented utilization to a significantly greater degree in the nucleus accumbens core. Clozapine increased dopamine utilization to an equivalent degree in both nucleus accumbens regions. Short duration immobilization stress selectively increased dopamine utilization in the nucleus accumbens shell. These data indicate that there are significant differences between the nucleus accumbens core and nucleus accumbens shell in basal dopamine metabolism, and indicate that the core and shell dopamine innervations can be distinguished on the basis of response to both pharmacological and environmental challenges. These data are consistent with the hypothesis that the dopaminergic innervation of the nucleus accumbens core is associated with the nigrostriatal system, while that of the nucleus accumbens shell is related to the mesolimbic system.

One experience with ‘lower’ or ‘higher’ intensity stressors, respectively enhances or diminishes responsiveness to haloperidol weeks later: implications for understanding drug variability

The laboratory has previously shown that acute exposure to a variety of brief stressful events can have a very long-lasting influence on subsequent responsiveness to pharmacological and non-pharmacological stressors. In some cases the response to these agents is enhanced, while in others it is diminished: the common denominator being that is each instance the influence of the initial stressor grows stronger with the passage of time. Here, we identify one factor that determines which time-dependent effect is maniffest. In 3 separate experiments, male rats were subjected to a single exposure to stressors of either lower or higher intensity and their effects on haloperidol-induced catelepsy and dopamine and dihydroxyphenylacetic acid levels in the nucleus accumbens and medial frontal cortex, measured either 1–2 h or 2 weeks later. The stressors were either environmental (needle jab or 1 h of immobilization), metabolic (200 or 750 mg/kg, i.p. of 2-deoxy- d-glucose), or pharmacological (0.5 g/kg or 2.0 g/kg, ethanol). Degree of stressfulness was indexed by measuring plasma corticosterone levels. There was no effect on haloperidol-induced catalepsy when stressors preceded such behavioral testing by 1–2 h. By contrast, when the interval was 2 weeks, the lower-intensity stressors all increased haloperidol catalepsy, whereas higher-intensity stressors decreased the same response. In other words, a process that progressed with the passage of time was observed regardless of whether sensitization or diminution of haloperidol's action occured. In contrast to the uniform bipolar behavioural effects observed, depending on the intensity of the prestressor, the neurochemical findings failed to show any evidence of bipolarity whatever. Instead, both environmental and pharmacological stressors induced long-term, generally time-dependent changes, suggestive of a persistent decrease in dopamine utilization, while our metabolic stressor had no effect. Our results demonstrate a stressor-induced, time-dependent process that either increases or decreases responsiveness to drugs, depending on the intensity of the earlier stressor. They may be relevant to the variability in response to drugs frequently encountered in both the experimental and clinical literatures.

Chronic continuous nicotine treatment causes decreased burst firing of nigral dopamine neurons in rats partially hemitransected at the meso-diencephalic junction

Chronic continuous administration of nicotine (0.125 mg/kg/h, 14 days) to male Sprague-Dawley rats with a partial hemitransection at the meso-diencephalic junction caused a significant reduction in burst firing of remaining dopamine (DA) neurons in the zona compacta, substantia nigra, whereas neither the firing rate nor the number of spontaneously active DA cells per track were altered in comparison with saline-treated, hemitransected controls. The reduced functional activity of the remaining DA cells subjected to nicotine treatment provides a physiological correlate to the previously observed, reduced DA utilization in these neurons. It may also help to explain the increased nigral DA cell survival found after chronic nicotine treatment in similar lesion experiments.

Time-dependent variations of central norepinephrine and dopamine following antigen administration

Administration of sheep red blood cells (10 6 cells, i.p.) resulted in central norepinephrine (NE) and dopamine (DA) changes which corresponded with the time of the peak immune response. These amine variations, however, appeared to be specific to certain brain regions. The increased accumulation of the NE metabolite, 3-methoxy-4-hydroxyphenylethylene glycol, was evident in hypothalamus, locus coeruleus and hippocampus and a moderate reduction of NE was evident in the hypothalamus. Alterations of DA levels or utilization appeared in mesocorticolimbic structures (i.e. nucleus accumbens and prefrontal cortex)but not in striatum. This profile of transmitter changes was reminiscent of that previously shown to be induced by uncontrollable stressors and the possibility was offered that antigenic challenge is interpreted as a stressor by the central nervous system.

Side and region dependent changes in dopamine activation with various durations of restraint stress

Exposure to various mild stressors has been shown to result in the activation of dopamine containing neuronal systems projecting to the medial prefrontal cortex (PFC), to a lesser extent the nucleus accumbens septi/olfactory tubercle (NAS) and, in a few studies, the striatum. It has also been shown that dopamine (DA) systems on different sides of the PFC are successively activated as stressors are prolonged. We have therefore examined the effects of variation in the duration of a restraint stressor (15, 30 and 60 min) on region and side dependent alterations in DA utilization in the PFC, NAS and striatum. Increases in the concentrations of the DA metabolites 3,4-dihydroxyphenylacetic acid (DOPAC) and/or homovanillic acid (HVA) or in their ratios with DA were seen in all regions examined with the largest effects occurring in the PFC and lesser effects in the NAS and striatum. In each region, the magnitude of these effects varied with time of restraint exposure. In the PFC, lateralized alterations in HVA and DA were seen over time with effects progressing from a left > right involvement at 15 min to a right > left involvement at 60 min. These results are discussed with reference to side and region dependent effects on brain DA systems as stressors are prolonged and the implications they may have for lateralized regional brain activity associated with stressor precipitated psychiatric disease.

On the role of neuropeptide Y receptors of the Y 2 type in the control of hypothalamic catecholaminergic mechanisms and neuroendocrine function. Central effects of the NPY fragment (13–36)

The effects of intracerebroventricular injections (i.v.t.) of increasing doses of porcine neuropeptide Y (13–36) [pNPY (13–36); 7.5 1250 pmol/rat] on catecholamine (CA) levels and turnover in discrete hypothalamic regions and on neuroendocrine function have been studied in the unanaesthetized, unrestrained male rat. Histofluorometrical methods in combination with tyrosine hydroxylase (TH) inhibition was used for determination of CA levels and utilization. The serum levels of the adenohypophyseal hormones prolactin, luteinizing hormone and growth hormone as well as corticosterone serum levels were determined. The pNPY (13–36) fragment in low doses (25 pmol) produced a reduction of CA utilization, probably mainly of dopamine (DA), in the medial and lateral palisade zone (MPZ and LPZ) of the median eminence. At the highest dose (1250 pmol) pNPY (13–36) instead reduced DA levels and increased DA utilization in LPZ without significantly affecting CA levels and utilization in the MPZ. Only NA nerve terminals of the anterior periventricular hypothalamic were affected by pNPY (13–36), showing a depletion of NA after doses of 75–250 pmol and a significant increase in NA utilization after the highest dose (1250 pmol/rat). pNPY (13–36) (75–750 pmol/rat) produced a reduction of corticosterone serum levels, and after the highest doses of pNPY (13–36) (750 and 1250 pmol/rat) the prolactin serum levels were significantly reduced. The growth hormone serum levels were significantly reduced after a low dose (25 pmol/rat) of pNPY (13–36). An increase of luteinizing hormone serum levels was observed after many of the high doses but only became significant with 750 pmol/rat. These data give indications for a complex regulation by NPY receptors of the Y 2 type of neuroendocrine function and of the tuberoinfundibular DA neurons and the NA nerve terminals of the posterior periventricular hypothalamic nucleus in unanaesthetized male rats. An inhibitory role of NPY receptors of the Y 2 type appears to exist in the central control of corticosterone, prolactin and growth hormone secretion in the adult male rat while a stimulating role exists in control of luteinizing hormone secretion. Although mainly non-CA mechanisms appears to be involved, it seems possible that the biphasic regulation of the tuberoinfundibular neurons by NPY receptors of the Y 2 type may contribute to their inhibitory regulation of prolactin and stimulatory regulation of luteinizing hormone secretion. Based on a comparison with pNPY (1–36) it seems possible that NPY Y 1 receptors instead are involved mainly in the stimulatory control of corticosterone and of prolactin secretion and the inhibitory control of luteinizing hormone secretion.

Neurochemical evaluation of the striatum in symptomatic and recovered mptp-treated cats

Striatal neurochemistry and motor activity were assessed in cats treated with l-methyl-4 phenyl-1,2,3,6-tetrahydropyridine (MPTP) and killed either when symptomatic for a Parkinson-like motor disorder or six weeks later, when showing significant motor recovery. The results of striatal neurochemical analyses showed distinct regional differences in susceptibility to MPTP-induced damage, with dorsal striatal regions generally more severely affected than ventral striatal regions. Symptomatic animals had more severe dopamine loss in all striatal regions than did recovered animals. The dorsal lateral caudate, the cat's sensorimotor striatum, had the largest dopamine depletion in the symptomatic animals (99%) and the least recovery in recovered animals (94% depletion). In contrast, the nucleus accumbens had a 94% dopamine depletion in symptomatic animals and only a 34% depletion in recovered animals. In addition to increases in dopamine levels and dopamine utilization in the striatum in recovered animals, significant increases in serotonin levels and serotonin utilization were also observed. Therefore, motor recovery may have been due to either or both of these neurochemical changes. The fact that the cat develops Parkinson-like motor symptoms but that they are not persistent may make this an interesting model in which to study the role of dopamine in motor function and to study compensatory mechanisms of the damaged dopamine system.

Effect of Panax ginseng on age-related changes in the spontaneous motor activity and dopaminergic nervous system in the rat.

Effects of Panax ginseng on the spontaneous motor activity and central dopaminergic systems in old rats were investigated and compared with those in young rats. Oral intake of a 1.8% water extract of Panax ginseng for four weeks produced an increase in spontaneous motor activity during the dark period in old rats, while it caused a decrease in the activity in young rats. After the intake of ginseng extract for five weeks, it caused a significantly low dopamine utilization in the daytime in the striatum of old rats, while it produced a high dopamine utilization in the structure of young rats. Concentrations of striatal dopamine D-2 receptors in old rats were significantly lower than that in young rats, although subchronic Panax ginseng did not affect the striatal D-1 and D-2 receptors of old rats. These results suggest that subchronic intake of ginseng extract inhibits the activity of nigro-striatal dopamine neurons in the daytime and activates spontaneous motor activity during the dark period in old rats, while it produces opposite effects in young rats.