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K Jhamandas

Publications and source records attributed to K Jhamandas.

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

Picolinic acid blocks the neurotoxic but not the neuroexcitant properties of quinolinic acid in the rat brain: evidence from turning behaviour and tyrosine hydroxylase immunohistochemistry.

Previous results suggest that the tryptophan metabolite, picolinic acid may have the unusual properties of antagonizing the neurotoxic but not the neuroexcitant effects of another tryptophan metabolite, quinolinic acid in the central nervous system. The present experiments tested this possibility utilizing behavioural and tyrosine hydroxylase immunohistochemical techniques. In the first series of experiments, rats received injections of relatively high concentrations of 6-hydroxydopamine (12 micrograms in 1 or 2 microliters), quinolinic acid (120 nmol in 0.5 microliters), picolinic acid (480 nmol in 0.5 microliters) or co-treatments (0.5 microliters) with quinolinic (120 nmol) plus picolinic acid (480 nmol) into the region of the substantia nigra. Results revealed that 6-hydroxydopamine and quinolinic acid alone produced a large loss of tyrosine hydroxylase-positive cells in the pars compacta of the substantia nigra. Behavioural results for all 6-hydroxydopamine (n = 10) and for some quinolinate-treated rats (n = 5) revealed ipsi- and contraversive circling following amphetamine (1 mg/kg, i.p.) and apomorphine (0.5 mg/kg, s.c.), respectively, consistent with unilateral loss of dopamine cells in the substantia nigra. The remaining quinolinate-treated rats (n = 9) circled ipsiversively following either stimulant suggesting damage to the pars reticulata. Groups treated with picolinic acid alone (n = 6) or co-injected (n = 6) showed no loss of tyrosine hydroxylase-positive cells in the substantia nigra and no circling response to the stimulants. In the second series of experiments, low concentrations of quinolinic acid (2.5, 5.0, 7.5 nmol), picolinic acid (10, 20, 30 nmol), or the two together (7.5 plus 30 nmol, respectively) were microinjected (0.5 microliter) into the dorsal striatum and circling behaviour evaluated. These results revealed dose-dependent contralateral circling with either quinolinate or picolinate; co-injection of the two tryptophan metabolites also produced contralateral circling. It was concluded that picolinic acid blocks the neurotoxic but not the neuroexcitant effects of quinolinic acid.

Animals↗
PubMed1994

Mnemonic deficits in the double Y-maze are related to the effects of nucleus basalis injections of ibotenic and quisqualic acid on choline acetyltransferase in the rat amygdala.

Many researchers have reported that the magnitude of decrease in cortical choline acetyltransferase (ChAT) following excitotoxic lesions of the nucleus basalis magnocellularis (nbm) is unrelated to the degree of cognitive impairment. Recently, an explanation has been offered for this lack of correlation: different excitotoxins, when injected into the nbm, differentially affected cholinergic projections to the cortex and amygdala, and those excitotoxins previously reported to produce the greatest mnemonic deficits produced the largest decreases in amygdaloid ChAT. The present study evaluated the role of amygdalofugal cholinergic projections in memory by comparing the effects of intra-nbm ibotenic and quisqualic acid on cortical and amygdaloid ChAT and on mnemonic performance in the double Y-maze. Rats were trained in the double Y-maze until working and reference memory choice accuracy stabilized to a criterion of > or = 78% correct. Rats then were given either bilateral quisqualic acid (60 nmol in 0.5 microliter), bilateral ibotenic acid (50 nmol in 0.5 microliter), or sham (0.9% saline in 0.5 microliter) lesions of the nbm, and again were tested on the maze. Quisqualate produced a selective impairment of working memory, a large (51%) decrease in cortical ChAT and a small (17%) decrease in amygdaloid ChAT; ibotenate, on the other hand, produced a greater impairment of working memory, an impairment of reference memory, a similar (51%) decrease in cortical ChAT, but a greater (30%) decrease in amygdaloid ChAT. These results suggest that the cholinergic projections from the nbm to the cortex and amygdala play an important role in memory. They suggest that excitotoxins producing greater depletions of amygdaloid ChAT produce greater mnemonic deficits.

Amygdala↗
PubMed1993

Picolinic acid modulates kainic acid-evoked glutamate release from the striatum in vitro.

Since picolinic acid, a tryptophan metabolite yielded by the kynurenine pathway, selectively attenuates quinolinic and kainic acid excitotoxicity that is dependent on the presence of a glutamatergic afferent input, it was hypothesized that this agent may inhibit the presynaptic release of glutamate. Using superfused rat striatal slices, this study examined the potential of picolinic acid, and related pyridine monocarboxylic acids, to modify kainic acid-induced glutamate release. Kainic acid (0.25, 0.5 and 1.0 mM) stimulated the release of glutamate, an effect which was calcium dependent and was attenuated in the presence of the kainate/AMPA receptor antagonist, 6,7-dinitroquinoxalene-2,3-dione (500 microM). Picolinic acid significantly decreased glutamic acid release evoked by exposure of striatal slices to 1 mM kainate in the presence of calcium. The inhibitory action of picolinic acid on kainate-induced release was also shared by nicotinic and isonicotinic acid. In the absence of external calcium, kainic acid-induced glutamate release was significantly reduced by approximately 65%. Under this condition, picolinic acid (100 microM) failed to influence kainic acid-induced release. Picolinic acid (100 microM) itself increased glutamate release by 35% over basal release. While the ability of picolinic acid to inhibit excitotoxin-induced release supports the notion that it may act presynaptically to modify excitotoxicity, lack of structural specificity in its action tends to cast doubt on this mechanism of action.

Animals↗
PubMed1993

Evidence for the involvement of excitatory amino acid pathways in the development of precipitated withdrawal from acute and chronic morphine: an in vivo voltammetric study in the rat locus coeruleus.

Previous studies have demonstrated that activation of excitatory amino acid (EAA) pathways projecting to the locus coeruleus may be involved in the increased firing of locus coeruleus (LC) neurons during opioid withdrawal. Using differential normal pulse voltammetry to monitor catechol oxidation current (CA.OC), an index of neuronal activity in the LC, the role of EAA pathways in naloxone precipitated withdrawal after acute and chronic morphine treatment was examined. Acute morphine treatment (10 micrograms i.c.v.) significantly reduced the CA.OC signal in the LC to 54.3 +/- 3.1% of baseline. Naloxone challenge (1 mg/kg i.v.) completely reversed the morphine effect and produced a significant increase in the CA.OC signal above baseline, peak 145.4 +/- 10.1% of baseline. This naloxone-induced rebound response was attenuated by pretreatment with the EAA receptor antagonists gamma-D-glutamylglycine (DGG) (2, 20, 200 micrograms i.c.v.) and (-)-2-amino-7-phosphonoheptanoic acid (D-APH), but not L-APH (25 micrograms i.c.v.). In chronically morphine-treated rats (25 micrograms/h i.c.v., 5 days), naloxone challenge (1 mg/kg i.v.) produced a significant increase in CA.OC signal, peak 466.5 +/- 112.7% of baseline. This naloxone-induced response was attenuated by pretreatment with DGG (200 micrograms i.c.v.) or D-APH (25 micrograms i.c.v.). To the extent that CA.OC reflects locus coeruleus neuronal activity, the present findings further suggest that increases in locus coeruleus activity during naloxone precipitated withdrawal after both acute and chronic morphine treatment are mediated at least in part by activation of EAA pathways.

2-Amino-5-phosphonovalerate↗
PubMed1993

Antinociceptive effects of intrathecally administered F8Famide and FMRFamide in the rat.

The effects of intrathecal injections of F8Famide (Phe-Leu-Phe-Gln-Pro-Gln-Arg-Phe-NH2, 0.05-17.5 nmol) and FMRF-amide (Phe-Met-Arg-Phe-NH2, 0.002-25 nmol), known as anti-opioid agents, were investigated by using noxious thermal (tail flick) and mechanical (paw pressure) tests in the rat. Both peptides produced significant long-lasting (24-48 h) analgesia in both tests without causing detectable motor dysfunction. Pretreatment with systemic naloxone (5.5 mumol/kg i.p.) attenuated the initial antinociceptive effects (first hour) induced by both peptides (8.8 nmol) in the tail flick test and only by FMRFamide in the paw pressure test. A subeffective dose of F8Famide (0.05 nmol) enhanced both the intensity and the duration of spinal morphine (6.6 nmol) analgesia in both tests. In contrast, a subanalgesic dose of FMRFamide (0.002 nmol) decreased the intensity and enhanced the duration of the effect of morphine. These results show that, besides acting as antinociceptive agents in the spinal cord, F8Famide and FMRFamide could differentially modulate spinal opioid functions.

Amino Acid Sequence↗
PubMed1993

Opioid and substance P receptor adaptations in the rat spinal cord following sub-chronic intrathecal treatment with morphine and naloxone.

The effect of continuous intrathecal infusion with morphine (5 mu/h) or naloxone (2 micrograms/h) was investigated with regard to analgesia and the apparent density of mu- and delta-opioid and neurokinin-I/substance P receptors in the rat spinal cord. Morphine infusion increased tail-flick and paw-pressure responses until day 4 after the mini-osmotic pump implant. A decline in antinociception, reflecting tolerance to morphine, was then apparent in both tests. Quantitative in vitro receptor autoradiography of [125I]FK-33824, [125I][D.Ala2]deltorphin-I and [125I] Bolton-Hunter substance P binding sites, as ligands of mu, delta and neurokinin-I/substance P receptors, respectively, was performed on lumbosacral spinal cord sections of seven-days tolerant animals. Treatments with morphine and naloxone induced a similar increase (37%) in the number of delta binding sites in the superficial laminae of the dorsal horn. In contrast, the density of mu-opioid receptors was only affected by naloxone (50% increase). Neurokinin-I/substance P binding parameters were not altered by these treatments. Thus, it appears that delta-opioid binding sites may be of special relevance with regard to the development of tolerance to opiates in the spinal cord.

Analgesics↗
PubMed1993

Scopolamine injected into the rat amygdala impairs working memory in the double Y-maze.

Recent neurochemical results suggest the hypothesis that the nucleus basalis magnocellularis (nbm) cholinergic projection to the amygdala may play a role in memory. The present study investigated the effects of intra-amygdaloid injections of the cholinergic antagonist scopolamine on working and reference memory in the double Y-maze. Rats were pretrained until working and reference memory choice accuracy stabilized to a criterion of > or = 86% correct. Bilateral cannulae were then surgically implanted in the basolateral amygdaloid complex. Rats (n = 9) received scopolamine in doses of 8.0, 24.0, and 72.0 micrograms/0.5 microliter and saline (0.5 microliter) in a counterbalanced order with retraining to criterion between injections. Intra-amygdaloid scopolamine produced a dose-dependent and differential impairment of working and reference memory. A dose of 24.0 micrograms impaired working memory without significantly affecting reference memory; doses of 8.0 micrograms and 72.0 micrograms affected neither and both types of memory, respectively. Results implicate amygdaloid acetylcholine in memory.

Amygdala↗
PubMed1993

Inhibition of spinal opioid antinociception by intrathecal beta-endorphin1-27 in the rat.

1. The effects of intrathecal (i.t.) administration of beta-endorphin and two shorter fragments, human and ovine beta-endorphin1-27, were examined for antinociceptive activity in the tail-flick and paw-pressure tests in the rat. Additionally, the ability of ovine beta-endorphin1-27 to influence the action of i.t. beta-endorphin, morphine and [D-Pen2-D-Pen5]enkephalin (DPDPE) was also examined in these tests. 2. After i.t. injection, beta-endorphin produced potent dose-related antinociception in the tail-flick and paw-pressure tests. Shorter endorphins produced much weaker effects. The order of antinociceptive efficacy was beta-endorphin > human beta-endorphin1-27 > ovine beta-endorphin1-27. 3. Administration of ovine beta-endorphin1-27 (0.72, 1.44 nmol, i.t.) significantly attenuated the antinociceptive effect of beta-endorphin (2.88 nmol, i.t.) in the tail-flick and paw-pressure tests. 4. Both i.t. morphine and DPDPE produced dose-related antinociception in the tail-flick and paw-pressure tests. The potency of DPDPE was lower than that of morphine in both tests; however, the effect of DPDPE was weaker in the paw-pressure test. 5. Administration of ovine beta-endorphin1-27 (1.44 nmol, i.t.) significantly attenuated the antinociceptive effect of morphine (14.9 nmol, i.t.) in both tests and the effect of DPDPE (38.7 nmol) in the tail-flick test. 6. The results show that beta-endorphin1-27 acts as an opioid antagonist at the spinal level in the rat. Its ability to inhibit the action of morphine and DPDPE suggests that it may attenuate beta-endorphin action by an interaction with mu- and/or delta-opioid receptors.

Analgesics↗
PubMed1992

Action of picolinic acid and structurally related pyridine carboxylic acids on quinolinic acid-induced cortical cholinergic damage.

Picolinic acid, a pyridine monocarboxylic acid derived from tryptophan metabolism by the kynurenine pathway, was shown to block cortical cholinergic neurotoxicity induced by quinolinic acid (QUIN), a pyridine dicarboxylic acid yielded by the same pathway. This study examined the specificity of the anti-toxic effect of picolinic acid by comparing its effect with several structurally related mono- and dicarboxylic acids, and by evaluating its potential to influence cholinergic neurotoxicity produced by kainic, ibotenic and quisqualic acid. Picolinic acid or related agents were injected alone or in combination with a fixed dose of QUIN into the right nucleus basalis magnocellularis (nbM) of rats anesthetized with halothane. Cholinergic neurotoxicity was assessed 7 days post injection by measuring choline acetyltransferase (ChAT) activity in the frontoparietal cortex on the injected and uninjected side. In picolinate experiments, the staining of nbM neurons by acetylcholinesterase (AChE) histochemistry was also examined. Focal injections of QUIN depleted cortical ChAT activity and staining of AChE in the nbM. Co-injection of picolinic acid with QUIN attenuated the decline in these two cholinergic neuron markers. Isonicotinate (4-pyridine monocarboxylate), but not nicotinate (3-pyridine monocarboxylate), significantly attenuated QUIN's effect on cortical ChAT activity. Among several dicarboxylic acids examined, only dipicolinate (2,6-pyridine dicarboxylate) showed activity. It produced a modest QUIN-like effect, but in co-injection experiments it attenuated the QUIN-induced decrease in cortical ChAT. When co-injected into the nbM with a neurotoxic dose of kainic, ibotenic or quisqualic acid which produced a neurotoxic response comparable to that of QUIN, picolinic acid attenuated kainic acid-induced neurotoxicity, but not ibotenate or quisqualate neurotoxicity.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

Muscimol injections into the nucleus basalis magnocellularis of rats: selective impairment of working memory in the double Y-maze.

Anatomical and neurochemical results suggest that the cortico- and amygdalopetal cholinergic neurons of the nucleus basalis magnocellularis (NBM) may receive GABAergic inputs. The present experiments were undertaken to evaluate the possible influence of intra-NBM injections of the GABAA agonist, muscimol, on memory. In two experiments, rats were chronically implanted with guide cannulae placed bilaterally into the NBM. Rats were trained to a criterion of at least 83% correct on each component in a double Y-maze task that allowed a dissociation of working and reference memory. The task began with placement into one of the two end arms of the first Y-maze and the reference memory task was to go to the stem for food. Access to the second Y was then given and the working memory task was to go to the goal arm opposite the arm in the first maze from which that trial began. In experiment 1, pre-trained rats (n = 7) received muscimol (0.5 microliter) in doses of 0, 0.01, 0.1 and 1.0 microgram in a counterbalanced order with re-training to criterion between injections. In experiment 2, pre-trained rats (n = 8) received saline, muscimol (0.1 microgram), the GABAA antagonist, bicuculline (0.01 microgram), and muscimol + bicuculline. Results of experiment 1 revealed that intra-NBM muscimol produced a dose-dependent and differential impairment of working and reference memory. A dose of 0.1 microgram impaired working memory without significantly affecting reference memory; doses of 0.01 microgram and 1.0 microgram affected neither and both types of memory, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

Stereoselective effects of central alpha 2-adrenergic agonist medetomidine on in vivo catechol activity in the rat rostral ventrolateral medulla (RVLM).

The stereoselective central effects of a novel, highly potent and selective alpha 2-agonist medetomidine on adrenergic neuronal activity, reflected by changes in catechol oxidation current, in the rostral ventrolateral medulla of the halothane-anesthetized rat were examined using in vivo differential normal pulse voltammetry. Dexmedetomidine, the active isomer, significantly decreased catechol oxidation current to 33.4 +/- 4.5% of baseline when given centrally (1 microgram, i.c.v.) and to 10.3 +/- 3.9% of baseline when given systemically (50 micrograms/kg, i.v.). Dexmedetomidine also significantly reduced mean arterial blood pressure by 19.9% following central administration but significantly increased mean arterial blood pressure by 59.9% following systemic administration. Levomedetomidine, the inactive isomer, had no effect on catechol oxidation current or blood pressure. The depressant effects of dexmedetomidine on catechol oxidation current were reversed by the selective alpha 2-adrenoceptor antagonist atipamezole (2 micrograms, i.c.v. or 200 micrograms/kg, i.v.). The results of the present study demonstrate, to our knowledge, for the first time the central stereoselective effects of medetomidine and antagonism by atipamezole on rostral ventrolateral medulla activity in the anesthetized rat.

Adrenergic alpha-Agonists↗
PubMed1992

Release of neuropeptide FF (FLFQPQRF-NH2) from rat spinal cord.

Neuropeptide FF (FLFQPQRF-NH2), originally isolated from bovine brain, is an FMRF-NH2-like peptide with morphine-modulating activity. Neuropeptide FF (NPFF) is highly localized in the dorsal spinal cords where there are also specific NPFF binding sites. Furthermore, there have been studies indicating that NPFF may participate in the regulation of pain threshold in the spinal cord. However, whether NPFF can be released from the spinal cord is not known. The present experiments, using an in vitro superfusion of an isolated whole rat spinal cord, demonstrated that high concentrations of KCl or substance P caused a release of NPFF immunoreactive material (IR) from the spinal cord into the perfusion medium in a calcium-dependent manner. Substance P (1-11) also produced a detectable release of NPFF-IR in vivo although the response was quite variable. The released NPFF-IR was analyzed by an HPLC study and found to consist of NPFF and other minor immunoreactive peptides. Further studies with substance P-related peptides showed that the in vitro release of NPFF-IR could also be induced by substance P (1-7) but not by [pGlu5,Me-Phe8,Sar9]-substance P (5-11) or substance K. These results suggest that the specific substance P receptor (SP-N), which is recognized by both substance P (1-11) and substance P (1-7) rather than the tachykinin receptor, is involved in NPFF secretion from the spinal cord. In view of the role of substance P (1-11) and substance P (1-7) in sensory transmission, the results of this study further support the role of NPFF in the modulation of antinociception in the spinal cord.

Amino Acid Sequence↗
PubMed1992

N-methyl-D-aspartate unilaterally injected into the dorsal striatum of rats produces contralateral circling: antagonism by 2-amino-7-phosphonoheptanoic acid and cis-flupenthixol.

To evaluate the possible contribution of dorsal striatal glutamate receptors to motor behavior, circling responses were observed in rats following unilateral intrastriatal microinjections of the agonist, N-methyl-D-aspartate (NMDA) or the antagonist, 2-amino-7-phosphonoheptanoic acid (APH). The role of dopamine (DA) in NMDA-produced circling also was evaluated. In experiment 1, an NMDA dose of 5.0 micrograms (in 0.5 microliter), but not 0.5 or 0.05 microgram produced significant contraversive circling. In experiment 2, an APH dose of 10.0 micrograms but not 1.0 or 0.1 microgram produced significant ipsiversive circling. In experiment 3, microinjection of the ineffective 0.1 microgram dose of APH or a dose (20 micrograms) of the DA antagonist, cis-flupenthixol, that did not produce circling when administered alone, significantly reduced the circling response produced by the 5.0 micrograms dose of NMDA. As NMDA produced circling in the same direction as that seen following similar unilateral injections of locomotion-stimulating DA agonists, the present results suggest that glutamate, acting via NMDA receptors in the dorsal striatum, may exert an excitatory influence on motor systems. The observation that a DA receptor blocker antagonized the NMDA response further suggests that the observed motor excitatory effect of glutamate at NMDA receptors requires concurrent stimulation of DA receptors in the same region of the striatum.

2-Amino-5-phosphonovalerate↗
PubMed1992

Excitotoxic lesions of rat basal forebrain: differential effects on choline acetyltransferase in the cortex and amygdala.

Previous studies have shown that basal forebrain lesions using different excitotoxins produce similar decreases in cortical choline acetyltransferase, but differential effects on memory. However, basal forebrain cholinergic neurons send efferents to the amygdala and cortex. The present studies compared the effects of several excitotoxins on choline acetyltransferase levels in both of these structures. Lesions of the basal forebrain were made in rats by infusing different doses of either alpha-amine-3-hydroxy-5-methyl-4-isoxazole propionic acid, ibotenic acid, quisqualic acid, quinolinic acid or N-methyl-D-aspartic acid and measuring choline acetyltransferase seven days later. All of the excitotoxins exerted a differential response on cholinergic neurons of the basal forebrain projecting to the cortex or amygdala. Quinolinic acid was a more potent neurotoxin to cholinergic neurons innervating the amygdala than those projecting to the cortex. In contrast, quisqualic acid and alpha-amine-3-hydroxy-5-methyl-4-isoxazole were more potent neurotoxins to the cortical projection. alpha-Amine-3-hydroxy-5-methyl-4-isoxazole propionic acid was the most potent excitotoxin for destroying cholinergic neurons innervating either the cortex or amygdala. A parallel neurotoxic response was obtained in the cortex and amygdala following infusion of ibotenic acid or N-methyl-D-aspartic acid with little selectivity for choline acetyltransferase depletion in the cortex or amygdala. Histological analysis of the injection site revealed that acetylcholinesterase-positive neurons were destroyed by the excitotoxins in a dose-dependent manner. Excitotoxins (ibotenic acid, quinolinic acid, N-methyl-D-aspartic acid) that produce the greatest impairments in memory were found to produce the greatest depletion of choline acetyltransferase in the amygdala.(ABSTRACT TRUNCATED AT 250 WORDS)

Amygdala↗
PubMed1992

Yohimbine-precipitated clonidine withdrawal: an experimental model of the antihypertensive drug withdrawal syndrome.

In this study, a model of the clonidine withdrawal syndrome in normotensive rats was used to investigate the mechanisms and sites of the cardiovascular responses associated with this withdrawal. Clonidine (400 micrograms.kg-1.day-1), an alpha 2-adrenergic receptor agonist, was administered to rats via indwelling osmotic minipumps for 7 days. Withdrawal was precipitated by an intravenous injection of the alpha 2-adrenergic receptor antagonist yohimbine under alpha-chloralose anaesthesia, and the blood pressure and heart rate responses were recorded. Yohimbine (0.25, 0.50, and 1.0 mg/kg i.v.) in clonidine-treated rats provoked an immediate rise in blood pressure and heart rate. Similar injections in saline-treated rats produced slight hypotension and modestly increased the heart rate. Intracerebroventricular (i.c.v.) yohimbine injection (30 or 120 micrograms/kg in 10 microL volume) failed to elicit signs of withdrawal in clonidine-treated animals, but a subsequent intravenous injection of yohimbine (0.5 mg/kg) provoked brisk signs of withdrawal. hexamethonium (2 mg/kg) pretreatment did not abolish the increase in the heart rate, but it delayed the blood pressure increase. Pretreatment with atropine sulfate (1 mg/kg) did not block the yohimbine-induced increase in heart rate or blood pressure. This study demonstrates that yohimbine can effectively produce cardiovascular signs of withdrawal in rats chronically exposed to clonidine. The lack of i.c.v. yohimbine suggests that the antagonist-precipitated withdrawal may not have a central origin.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

In vivo catechol activity in the rat locus coeruleus following different nociceptive stimuli and naloxone.

The nucleus locus coeruleus (LC) has been implicated in the processing of spinal reflexes following noxious stimuli. It has been demonstrated that noxious stimuli activate LC neuronal firing, but little is known about the neurochemical changes that might occur following such activation. To determine the effects of different noxious stimuli on LC neuronal activity, anaesthetized rats were exposed to mechanical (tail pinch), thermal (55 degrees C water), and chemical (5% Formalin injected in the hind paw) stimuli; the catechol oxidation current (CA.OC), an index of noradrenergic neuronal activity, in the locus coeruleus was monitored using differential normal pulse voltammetry. In addition, the effect of the opioid antagonist naloxone on the CA.OC in the LC was examined. Exposure to both mechanical and chemical stimuli significantly increased CA.OC indicating an increase in LC noradrenergic neuronal activity, while the thermal stimulus had no effect. Treatment with naloxone (1 mg/kg i.v.) had no effect on CA.OC in the LC. The results show a differential responsiveness of LC noradrenergic neurons to different modes of noxious stimuli and fail to demonstrate a tonic opioid regulation of these neurons in the anaesthetized rat.

Animals↗
PubMed1991

Quinolinic acid elevates striatal and pallidal Met-enkephalin levels: the role of enkephalin synthesis and release.

Huntington's chorea (HC) is characterized, in part, by a substantial deficit in the striatal and pallidal enkephalin levels. Recently, an attempt was made to replicate this deficit by focally injecting quinolinic acid (QUIN), an excitotoxin, into the rat striatum. However, at 7 days post-injection, QUIN produced a dose-related and bilateral increase in the striatal and pallidal levels of met-enkephalin-like immunoreactivity (ME-i.r.), an effect which was attenuated in the presence of excitatory amino acid (EAA) receptor antagonists. In the present study, the action of QUIN was investigated further. To determine whether the QUIN (72 nmol)-induced elevations in ME-i.r. reflected the enhanced synthesis of the peptide, the striatal levels of proenkephalin mRNA were assayed 7 days following a unilateral injection of QUIN into the rat striatum. QUIN significantly depleted (50%) of the proenkephalin mRNA level in the injected, but not the contralateral striatum when compared to that in the saline-injected animals. To determine whether the QUIN-induced increases in ME-i.r. were due to an impaired release of the peptide, the release of ME-i.r. from the striatal or pallidal slices obtained from animals 7 days after a saline- or QUIN-injection, was measured. The 30 mM K(+)-stimulated ME-i.r. release from the saline-injected and contralateral striatum represented an 8-fold increase above the spontaneous release level, while this stimulus induced a 6-fold increase in the ME-i.r. release from both the QUIN-injected and contralateral striatum.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗