PubMed Health⌕ Search

Biomedical subjects

L A Chiodo

Publications and source records attributed to L A Chiodo.

At least 55 records · Page 3Linked to original sources
PubMed1989

D1 receptor activation enhances sciatic nerve stimulation-induced inhibition of nigrostriatal dopamine neurons.

Nigrostriatal dopamine (NSDA) neurons have been hypothesized to play an important regulatory role in neostriatal sensorimotor integration. In order to provide further information on the nature of sensory modulation of NSDA cells, we have examined the pharmacology of the responsiveness of these neurons to peripheral nerve stimulation. The selective D1 dopamine receptor agonist SKF 38393 enhanced the normal inhibition of NSDA neurons produced by electrical stimulation of the sciatic nerve. The SKF 38393-induced enhancement, but not the basal stimulation-induced inhibition itself, was blocked by prior hemitransection of the forebrain and was reversed by the selective D1 antagonist SCH 23390 but not by the selective D2 antagonist 1-sulpiride. SCH 23390 alone, however, exerted no effect on this inhibition. The selective D1 receptor agonist fenoldopam, which does not cross the blood-brain barrier, also failed to alter the response to sciatic nerve stimulation (i.v. administration). Thus, central D1 receptors (rostral to the midbrain) appear to be involved in a system which mediates phasic control over sensory modulation of NSDA neuronal activity.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗
PubMed1989

Medial forebrain bundle stimulation or D-2 dopamine receptor activation increases preproenkephalin mRNA in rat striatum.

Electrical stimulation of the medial forebrain bundle, in a manner that augmented the release of dopamine in the forebrain, rapidly increased the striatal content of preproenkephalin (but not preprotachykinin) mRNA. This effect was mimicked by administration of either the indirect (dopamine-releasing) agonist methamphetamine or by the D-2 dopamine receptor agonist quinpirole, but not by the D-1 agonist SKF 38393. These data suggest that D-2 receptors, which mediate a stimulatory effect on enkephalin gene expression, may be subsaturated under basal conditions and, therefore, responsive to increases in synaptic dopamine.

Animals↗
PubMed1989

Electrophysiological characteristics and pharmacological responsiveness of midbrain dopaminergic neurons of the aged rat.

The extracellular electrophysiological activities of A9 and A10 dopaminergic (DA) neurons were examined in chloral hydrate-anesthetized young (3 months) and aged (24-28 months) Fischer 344 male rats. Average firing rate, firing rate distribution and the incidence of spontaneous activity (cells per electrode track) did not change in either region as a function of age. Next, the inhibitory effects of several DA agonists on the firing rates of antidromically identified nigrostriatal DA cells were compared in young and old rats. The inhibitory potencies of i.v. apomorphine (D1/D2 agonist), quinpirole (D2 agonist) and d-amphetamine (indirect agonist) did not change with age. Similarly, the inhibitory effects of microiontophoretically applied dopamine were unaltered in aged rats. Stimulation of the sciatic nerve resulted in brief periods of inhibition of the activity of nigrostriatal DA neurons in both the young and the old age groups. The duration of this inhibitory response was, however, enhanced markedly in the old rats. The D1 agonist SKF 38393 enhanced the duration of the inhibitory effect of sciatic nerve stimulation in both young and old rats. These results suggest that, although no gross differences in the activity of DA cells in young and old rats were evident, subtle changes in the regulation of the activity of these neurons may occur with age.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗
PubMed1989

CI-943, a potential antipsychotic agent. III. Evaluation of effects on dopamine neuronal activity.

CI-943 (8-ethyl-7,8-dihydro-1,3,5-trimethyl-1H-imidazo[1,2- c]pyrazolo[3,4-e]pyrimidine) has been identified as a novel potential antipsychotic agent that does not bind to dopamine (DA) receptors. In the present studies, the effects of acute and chronic administration of CI-943 on the electrophysiological activity of A9 and A10 DA neurons were assessed and compared to the effects of DA antagonist antipsychotic drugs. Acute administration of CI-943 did not increase the base-line firing rate (10-20 mg/kg i.p.), did not increase the number of spontaneously active DA neurons (40 mg/kg p.o.) and did not antagonize the effects of apomorphine or amphetamine on A9 or A10 DA neurons (20-40 mg/kg i.p.). A high dose of CI-943 (40 mg/kg i.p.) decreased the firing rate of A9 and A10 DA neurons, an effect that was not antagonized by haloperidol. In contrast, haloperidol increased the base-line firing rate (0.5 mg/kg i.p.), increased the number of spontaneously active DA neurons (0.5 mg/kg p.o.) and antagonized the effects of apomorphine and d-amphetamine on A9 and A10 DA neurons (0.1 mg/kg i.p.). Repeated (21 days) administration of CI-943 (36 mg/kg/day p.o.) did not alter the number of spontaneously active A9 DA neurons but increased the number of active A10 DA neurons. In contrast, repeated administration of haloperidol (0.4 mg/kg/day p.o.) decreased the number of spontaneously active DA neurons in A9 and A10, whereas repeated administration of clozapine (19 mg/kg/day p.o.) decreased the number of active A10 DA neurons but increased the number of active A9 DA neurons.(ABSTRACT TRUNCATED AT 250 WORDS)

Action Potentials↗
PubMed1988

Electrophysiological effects of cholecystokinin octapeptide on identified rat nigrostriatal dopaminergic neurons.

Cholecystokinin octapeptide (CCK-8) exists in a subpopulation of midbrain dopaminergic (DA) neurons and has been shown to affect the activity of unidentified DA cells. This study describes the effects of the sulfated (CCK-8S) and unsulfated (CCK-8US) peptides (8 micrograms/kg, i.v.) on the ability of apomorphine to inhibit the firing rate of nigrostriatal DA cells identified by antidromic activation from the caudate nucleus of anesthetized rats. CCK-8S excited 9/25 DA cells while CCK-8US was without effect on firing rate (n = 9). CCK-8S pretreatment resulted in complex changes in the sensitivity of nigrostriatal DA cells to apomorphine which were related to whether an initial excitatory response was elicited by CCK-8S. CCK-8US did not alter apomorphine sensitivity. These results suggest that CCK-8S can exert modulatory effects on DA cells independent of a direct excitatory action. The effect of acute CCK-8 injection on the number of spontaneously active DA cells in stereotaxically defined regions of the substantia nigra and ventral tegmental area was also determined. CCK-8S doubled the number of active cells in these areas; CCK-8US did not alter the population activities.

Animals↗
PubMed1988

SKF 38393 alters the rate-dependent D2-mediated inhibition of nigrostriatal but not mesoaccumbens dopamine neurons.

Previous electrophysiological studies have failed to identify significant effects of the D1 dopamine (DA) agonist SKF 38393, either alone or in combination with the D2 agonist quinpirole (LY 171555), on the spontaneous firing rate of midbrain DA neurons. We have utilized extracellular single-unit recording techniques to examine whether SKF 38393 can alter D2-mediated inhibition of DA cell activity. Quinpirole-induced inhibition of the spontaneous activity of midbrain DA neurons was observed to be positively correlated with the basal firing rate of the neuron being examined (i.e., faster cells required higher doses to achieve 50% and maximal inhibition). Pretreatment with SKF 38393 (1.0 mg/kg, i.v.; 4 minutes) eliminated the rate dependency of quinpirole-induced inhibition of nigrostriatal but not mesoaccumbens DA neurons. This effect of SKF 38393 was blocked both by the D1 antagonist SCH 23390 and by hemitransections of the forebrain. In summary, SKF 38393 appears to exert Dl-specific, feedback pathway-dependent effects on the profile of responsiveness of nigrostriatal DA neurons to D2-mediated inhibition of cell firing rate.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗
PubMed1988

Electrophysiological and pharmacological characterization of identified nigrostriatal and mesoaccumbens dopamine neurons in the rat.

Extracellular single-unit recording techniques were used to compare the basal activity and pharmacological responsiveness of identified nigrostriatal and mesoaccumbens dopamine (DA)-containing neurons. The projection area of each DA cell was determined by antidromic activation techniques. The forebrain stimulation used for the cell identification procedure did not alter the pharmacological responsiveness of DA neurons; the inhibitory effect of apomorphine (and d-amphetamine) was identical when stimulation was applied either prior to or following drug administration. Analysis of the spike discharge pattern revealed that a higher proportion of mesoaccumbens DA cells exhibited burst-firing activity. Although the firing pattern of the two populations of burst-firing DA cells was similar in many regards, mesoaccumbens DA cells exhibited a longer postburst inhibition than did nigrostriatal DA cells. Each of the DA agonists, apomorphine, pergolide, B-HT 920, and d-amphetamine, inhibited nigrostriatal and mesoaccumbens DA neuronal activity in a similar fashion. However, there was a marked population difference in the recovery of cell firing in the 10 minutes following apomorphine-induced inhibition; the recovery of mesoaccumbens spike discharges was considerably slower. Although this population difference was apparent to some extent following administration of pergolide or B-HT 920 (but not d-amphetamine), it was considerably less marked. The present findings are discussed with respect to the known regulatory control of midbrain DA neurons.

Action Potentials↗
PubMed1988

Dopamine-containing neurons in the mammalian central nervous system: electrophysiology and pharmacology.

A decade of research culminated in the late 1950's with the demonstration that dopamine was a chemical neurotransmitter within the mammalian brain. Since this time, dopaminergic neuronal systems have been extensively studied using numerous techniques. This paper will review the last 14 years of electrophysiological investigation on neurochemically identified dopamine-containing neurons in the central nervous system. This will include an examination of both the electrophysiological and pharmacological characteristics in these cells, as well as the resulting insights into the regulation of dopamine cell electrical activity which is derived from this work.

Animals↗
PubMed1987

Electrophysiological studies on the specificity of the cholecystokinin antagonist proglumide.

Recent evidence suggests that the glutaramic acid derivative proglumide (PROG) is a selective antagonist of cholecystokinin (CCK) in the rat CNS. The extent of this selectivity has now been characterized in more detail. Iontophoretic or intravenous (i.v.) administration of PROG was ineffective against the excitatory effect of iontophoretically applied neurotensin on midbrain dopamine (DA) cells, the excitatory effect of substance P and the inhibitory effect of Met-enkephalin on prefrontal cortical neurons, and the inhibitory effect of histamine on neurons of the sensorimotor cortex. In contrast, PROG blocked the excitatory effect of the C-terminal octapeptide of CCK in all 3 areas. Furthermore, iontophoretic PROG diminished, whereas CCK enhanced the inhibitory effect of similarly applied DA and GABA on DA cells. PROG pretreatment (1 mg/kg, i.v.) reduced the inhibitory potency and maximum effect of i.v. apomorphine (APO) on A9 DA neurons, while the inhibitory potency of APO was enhanced by i.v. CCK. Pretreatment with PROG plus CCK resulted in APO effects which were no different from those after PROG alone. Chronic treatment with PROG (1 mg/kg, p.o., 21 days) resulted in a return to normal of DA cell APO sensitivity. Combined, these findings suggest that PROG may be a relatively selective CCK antagonist, that the functional effect of dendritically released DA may be influenced by endogenously released CCK, and that tolerance may develop to the effects of chronic CCK receptor blockade.

Action Potentials↗
PubMed1987

Population response of midbrain dopaminergic neurons to neuroleptics: further studies on time course and nondopaminergic neuronal influences.

In the present study, we examined the effects of the cholecystokinin receptor antagonist, proglumide, on the depolarization-induced inactivation of A9 and A10 dopaminergic neurons produced by repeated administration of a classical antipsychotic drug (dopamine receptor antagonist). In addition, we studied the nature of the effects of acute (1-48 hr) and long-term (7 month) treatment with the butyrophenone neuroleptic haloperidol on both the basal firing rate and population response of dopamine-containing neurons in these 2 regions. Acute oral administration of haloperidol (0.5 mg/kg) results, within 1 hr of administration, in an increase in both the firing rate and number of spontaneously active dopamine neurons encountered in both A9 and A10 regions. These effects of a single treatment persist for a minimum of 6 hr and, with respect to firing rate, are not completely normalized for at least 24 hr. In contrast, 7 month continuous treatment with haloperidol reduces the number of spontaneously active DA neurons encountered in both regions in a manner similar to that observed at 21 d. This effect is inferred to be due to the induction of depolarization-induced inactivation of these neurons, since the acute administration of the normally hyperpolarizing, direct-acting dopamine receptor agonist apomorphine (64 micrograms/kg) immediately reverses this reduced number of cells per track to near control levels. This effect appears to be dependent on the continued presence of haloperidol since, when animals treated for 7 months are sampled 14 d after the cessation of drug administration, spontaneous activity is no different from that observed in age-matched controls.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1986

Interactions between dopamine and amino acid-induced excitation and inhibition in the striatum.

Iontophoretic techniques were used to examine the effect of dopamine on glutamate-induced excitation and gamma-aminobutyric acid (GABA)-induced inhibition of single striatal neurons in rat brain. When dopamine was applied at concentrations that produced little or no inhibition of spontaneous firing rate, both glutamate-induced excitation and GABA-induced inhibition were enhanced. In contrast, when dopamine was applied at doses that significantly decreased spontaneous firing, glutamate-induced excitation was greatly reduced, though GABA-mediated inhibition remained enhanced. Thus, dopamine acts to modulate the efficacy of other neurotransmitters impinging on striatal neurons, but has a qualitatively different effect on the excitatory activity of striatal cells depending on its concentration.

Animals↗
PubMed1985

Possible mechanisms by which repeated clozapine administration differentially affects the activity of two subpopulations of midbrain dopamine neurons.

Extracellular single-cell recording techniques were employed to study the mechanism of action of repeated oral clozapine administration on the in vivo spontaneous activity of substantia nigra (A9) and ventral tegmental area (A10) dopamine (DA)-containing neurons in the rat. Clozapine was observed to affect DA neurons differentially within these two regions when compared to haloperidol. Acute treatment (1 hr) with both drugs increased the number of spontaneously firing neurons in both A9 and A10. Chronic (21 day) treatment with haloperidol decreased the number of cells encountered in both regions, whereas repeated treatment with clozapine reduced the number of DA cells per track only in A10. In all cases, the silent DA neurons were inferred to be in a state of depolarization inactivation since they could be induced to discharge normally by the microiontophoretic application of the inhibitory neurotransmitter gamma-aminobutyric acid. These effects were not due to an effect of chloral hydrate anesthesia since they were also observed in gallamine-paralyzed, artificially respired animals. Chronic co-administration with haloperidol of either an anticholinergic (trihexyphenidyl) or the alpha 1-norepinephrine (NE) receptor antagonist, prazosin, but not an alpha 2-NE antagonist, RX781094, resulted in a differential effect on A9 and A10 DA neurons identical to that observed with repeated clozapine administration alone. Thus, chronic treatment with these combinations of drugs resulted in the depolarization inactivation of only A10 cells. These data suggest that anticholinergic and/or alpha 1-NE-blocking properties of clozapine may, in part, mediate its differential effects on A9 and A10 midbrain DA neurons.

Anesthetics↗
PubMed1984

Evidence for the absence of impulse-regulating somatodendritic and synthesis-modulating nerve terminal autoreceptors on subpopulations of mesocortical dopamine neurons.

Electrophysiological and biochemical techniques were used to study midbrain dopamine systems. In the electrophysiological studies, projection areas of individual dopaminergic cells were identified by antidromic activation. Dopamine cells which innervate the piriform cortex and those that innervate the caudate nucleus demonstrated their usual dose-dependent inhibitory response to both the intravenous administration of the direct-acting dopamine agonist apomorphine and the microiontophoretic application of dopamine. In contrast, the firing rate of dopamine neurons which project to the prefrontal cortex and of those terminating in the cingulate cortex was not altered by either the intravenous administration of low to moderate doses of apomorphine or microiontophoretically applied dopamine. The mean basal discharge rate and degree of burst firing was also different between these subgroups of midbrain dopaminergic neurons. Mesoprefrontal and mesocingulate dopamine neurons had mean firing rates of 9.3 and 5.9 spikes/s respectively, and showed intense burst activity. Mesopiriform and nigrostriatal dopamine cells had discharge rates of 4.3 and 3.1 spikes/s and displayed only moderate bursting. The dopaminergic nature of those mesocortical neurons insensitive to apomorphine and dopamine was confirmed using combined intracellular recording and catecholamine histofluorescence techniques. Thus, after the intracellular injection of colchicine and subsequent processing for glyoxylic acid-induced histofluorescence, the injected cells could be identified by their brighter fluorescences compared to the surrounding, normally fluorescing, non-injected dopamine neurons. Using biochemical techniques, subgroups of midbrain dopaminergic systems were again found to differ. The administration of gamma-butyrolactone increased dopamine levels in all areas sampled (prefrontal, cingulate and piriform cortices as well as the caudate nucleus). However, although this effect was readily reversed in both the piriform cortex and caudate nucleus by pretreatment with apomorphine, this treatment had no effect on the increased dopamine levels observed in the prefrontal and cingulate cortices. In addition, the decline in dopamine levels after synthesis inhibition with alpha-methyltyrosine was significantly faster in the prefrontal and cingulate cortices relative to the caudate nucleus. The piriform cortex showed an intermediate decline which was not significantly different from that observed in any of the other regions.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1983

Amitriptyline sensitization of a serotonin-mediated behavior depends on the passage of time and not repeated treatment.

Daily treatment for 10 days with either amitriptyline or the tricyclic muscle relaxant, cyclobenzaprine, increased the incidence of head-twitch behavior in response to 5-hydroxytryptophan (5-HTP) when this was examined two days later. Only one day of amitriptyline treatment followed by an 11-day hiatus before administration of 5-HTP also sensitized the head-twitch response whereas similar amitriptyline treatment followed by 5-HTP one hour later failed to do so. These data provide the first evidence for time-dependent sensitization of brain serotonin systems.

5-Hydroxytryptophan↗
PubMed1983

Subtotal destruction of central noradrenergic projections increases the firing rate of locus coeruleus cells.

The intraventricular administration of 6-hydroxydopamine was used to destroy 80-90% of the noradrenergic terminals in the forebrain of male rats with little apparent damage to the cells of origin in locus-coeruleus. Both 36 h and 21 days later the basal firing rate of these cells was elevated 4-fold above control levels. Moreover, microiontophoretic application of norepinephrine was significantly less effective in inhibiting the spontaneous activity of locus coeruleus cells in these rats relative to control animals. The increased firing may represent a compensatory response to the injury, leading to increased transmitter release release from terminals spared by the lesion.

Animals↗
PubMed1983

Proglumide: selective antagonism of excitatory effects of cholecystokinin in central nervous system.

Extracellular single-unit recording techniques were used to test the ability of proglumide to block cholecystokinin-induced excitation of rat midbrain dopaminergic neurons and dopamine-sensitive prefrontal cortex cells. Intravenous and iontophoretic proglumide administration consistently blocked cholecystokinin-induced excitations while having no effect on glutamic acid-induced increases in activity. This selective blockade of central cholecystokinin effects by proglumide suggests that this drug may be valuable for studying the possible role of cholecystokinin as a neurotransmitter or neuromodulator in the central nervous system.

Animals↗
PubMed1983

Electrophysiological studies on EMD 23 448, an indolyl-3-butylamine, in the rat: a putative selective dopamine autoreceptor agonist.

Single unit electrophysiological and microiontophoretic techniques were used to study the effects of a putative selective dopamine autoreceptor agonist, EMD 23 448, an indolyl-3-butylamine on the activity of both dopamine neurons in the substantia nigra and dopamine-sensitive neurons in the caudate nucleus. Intravenous administration of EMD 23 448 inhibited the firing of dopamine neurons in the nigra in a dose-dependent manner. This effect could be readily reversed by the subsequent intravenous administration of the dopamine receptor antagonist, haloperidol. Microiontophoretic application of EMD 23 448 onto these neurons also inhibited their activity and this effect was blocked by iontophoresis of the dopamine receptor antagonist, trifluoperazine. Intravenous administration of the former compound increased the activity of dopamine-sensitive cells in the caudate in the same doses which inhibited dopamine neurons in the nigra. However, this effect appeared to be indirect since the iontophoretic application of EMD 23 448 directly onto caudate neurons had no effect on their firing rate. In addition, the activity of norepinephrine-containing neurons in the locus coruleus and serotonin-containing cells in the dorsal raphé nucleus was not changed by direct microiontophoretic application of this compound. In contrast, EMD 23 448 selectively blocked the acetylcholine-induced activation of pyramidal neurons in the hippocampus. These findings provide further evidence that with respect to central catecholamine neurons EMD 23 448 may be a selective agonist for dopamine autoreceptors.

Acetylcholine↗