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A S Freeman

Publications and source records attributed to A S Freeman.

At least 37 records · Page 2Linked to original sources
PubMed1992

Acute effects of sigma ligands on the electrophysiological activity of rat nigrostriatal and mesoaccumbal dopaminergic neurons.

The effects of acute i.v. administration of several sigma ligands on the single-unit activity of nigrostriatal and mesoaccumbal dopaminergic (DA) neurons were evaluated in chloral hydrate-anesthetized rats. DTG (1,3-di(o-tolyl)guanidine) did not alter DA neuronal activity at nontoxic doses and JO 1784 [(+)-N-cyclopropylmethyl-N-methyl-1,4-diphenyl-1-ethylbut-3-en-1-+ ++ylamine] was inactive. (+)-Pentazocine was more effective in increasing mesoaccumbal vs. nigrostriatal DA cell firing rates. BMY 14802(alpha-(4-fluorophenyl)-4-(5-fluoro-2-pyrimidinyl)-1-piperazine-but anol) dose-dependently increased DA cell firing rate in both populations. The inhibition of nigrostriatal DA cell firing rate by (+)-3-(3-hydroxyphenyl)-N-(1-propyl)piperidine [(+)-3-PPP] was reversed by (-)-eticlopride and (+)-but not (-)-butaclamol, which supports previous evidence that (+)-3-PPP-induced inhibition is due to the DA agonist properties of the drug. From what is known of the pharmacological properties of these compounds, it is concluded that acute sigma receptor occupation does not markedly alter the firing rate of DA neurons. The dose-response curve for inhibition of nigrostriatal DA neuronal activity by the D2 DA agonist, quinpirole, was shifted to the right tenfold by BMY 14802 pretreatment (8 mg/kg, i.v.) and twofold by (+)-pentazocine (8 mg/kg, i.v.), but was not changed by DTG (2 mg/kg, i.v.). It is concluded that the marked effects of certain sigma ligands on DA cell electrophysiology are likely due to their non-sigma properties.

Animals↗
PubMed1992

Effects of supplemental protein percentage and feeding level on intake, ruminal fermentation, and digesta passage in beef steers fed prairie hay.

Twelve ruminally cannulated steers (average initial BW 357 kg) were allotted to four treatments (three steers per treatment) in a replicated 4 x 4 Latin square design with 21-d periods (12 d for adaptation and 9 d for collection) to compare the effects of protein supplements that differed in percentage of CP and feeding level on low-quality forage utilization. Treatments were 1) control (C), ad libitum access to 5.6% CP prairie hay, 2) C +600 g of DM.steer-1.d-1 of a 43% CP supplement based on cottonseed meal (PS), 3) C + 1,200 g of DM.steer-1.d-1 of a 22% CP supplement based on corn grain and cottonseed meal (GS), and 4) C + 600 g of DM.steer-1.d-1 of a 22% CP supplement based on corn grain and cottonseed meal (LS). Ruminal total VFA concentrations were increased 8% (P less than .07) by PS vs GS 1 h after supplementation. Among supplemented steers, ruminal acetate (mol/100 mol) was decreased 1.2 mol/100 (P less than .03) by GS vs PS and LS; however, supplementation did not affect (P greater than .10) acetate proportions compared with C. Neither propionate nor butyrate was affected (P greater than .10) by supplementation, but among supplemented steers, butyrate proportions were 8% greater (P less than .03) for GS than for PS and 5% less (P less than .10) for LS than for the average of GS and PS. Ruminal pH did not differ (P greater than .10) among treatments. Ruminal ammonia concentrations were increased 1.4 to 4.8 mg/100 mL (P less than .07) by supplementation and typically were less for LS than for PS and GS at most sampling times. Prairie hay DMI (average = 16.3 g/kg BW) was not affected (P greater than .10) by supplementation. Fluid dilution rate was 8% faster (P less than .01) when steers were supplemented than when they were not fed supplement, and fluid dilution rate was increased 4% (P less than .04) by GS compared with PS. Particulate digesta passage rate was not affected (P greater than .10) by treatment, but total tract retention time was decreased (P less than .01) 10% by supplementation. Extent and rate of prairie hay NDF digestion in situ were not greatly affected by supplementation, but in situ disappearance of supplement N was 6 to 10 percentage units less (P less than .06) for GS than for PS and 2 to 6 percentage units less for LS than for the average of PS and GS supplements.(ABSTRACT TRUNCATED AT 400 WORDS)

Ammonia↗
PubMed1991

Release of cholecystokinin from rat midbrain slices and modulatory effect of D2DA receptor stimulation.

Cholecystokinin octapeptide (CCK-8) is colocalized within a majority of dopamine (DA)-containing neurons of the rat midbrain. Exogenous CCK-8 can modulate the electrophysiological activity of DA neurons, at least in part, by direct actions on the somatodendritic region of these cells. If CCK-8 is somatodendritically released from DA neurons, it may influence DA cell function as has been shown for DA itself. In the present study, radioimmunoassay was used to determine if CCK-8 is released in vitro from slices of rat midbrain under basal and depolarizing (30 mM potassium) conditions. Low levels of CCK-8 were detected in the basal incubation medium. Thirty mM potassium caused about a 3-fold increase in the release of CCK-8. This stimulated release was abolished in calcium-free medium. The D2 receptor agonist quinpirole, but not the D1 agonist SKF 38393, attenuated the potassium-stimulated release of CCK-8 but did not affect basal release. These results show that CCK-8, like DA, can be released from midbrain slices, presumably from DA/CCK-8-containing neurons. This finding is in accordance with the possibility that CCK-8 plays a role in the regulation of DA neuronal function at the level of the cell body, where it might influence the excitability of the DA cell membrane.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗
PubMed1991

Receptor selectivity of cholecystokinin effects on mesoaccumbens dopamine neurons.

Extracellular recording techniques were combined with antidromic stimulation to examine the effects of C-terminal cholecystokinin (CCK) fragments and CCK antagonists on the activity of identified mesoaccumbens dopamine (MADA) neurons in chloral hydrate-anesthetized rats. These experiments were designed to determine the receptor selectivity of sulfated CCK octapeptide (CCK-8S) effects on MADA cells. Neither CCK tetrapeptide (CCK-4) nor unsulfated CCK octapeptide (CCK-8U) significantly altered MADA cell basal firing rate or responsiveness to the inhibitory effects of the D2 DA agonist quinpirole. As reported previously for ventral tegmental area DA cells, CCK-8S produced increases or decreases in the firing rate of most MADA cells sampled. CCK-8S also enhanced the sensitivity of MADA neurons to quinpirole-induced inhibition. This increase in sensitivity to quinpirole was blocked by pretreatment with the nonselective CCK receptor antagonist proglumide and the preferential CCK-A receptor antagonist CR 1409 but not by the preferential CCK-B receptor antagonist L-365,260. The inactivity of CCK-4 and CCK-8U in these tests and the results with the antagonists suggest that the effects of CCK-8S on MADA neuronal activity are mediated by CCK-A receptors.

Animals↗
PubMed1991

Dissociative anesthesia and striatal neuronal electrophysiology.

Compared with results obtained in locally anesthetized, paralyzed rats, the dissociative anesthetic ketamine did not alter either the number of spontaneously active striatal neurons or the basal firing rate of striatal neurons; 90% of these cells exhibited the type I striatal neuron waveform. Chloral hydrate anesthesia suppressed both the occurrence and the firing rate of spontaneously active type I cells, but did not alter the activity of type II striatal neurons. Cortical stimulation preferentially activated type II cells in paralyzed rats and in chloral hydrate-anesthetized rats. Thus, under dissociative anesthesia it is possible to study spontaneously active type I striatal neurons. However, a method of activation such as cortical stimulation is necessary to study type II striatal neurons.

Anesthesia, General↗
PubMed1991

Repeated SKF 38393 and nigrostriatal system neuronal responsiveness: functional down-regulation is followed by up-regulation after withdrawal.

The effects of chronic administration of the D1 dopamine (DA) agonist SKF 38393 on the basal activity and electrophysiological and pharmacological responsiveness of nigrostriatal DA neurons were examined by means of extracellular, single-unit recording techniques. Chronic D1 stimulation failed to alter either the basal activity of DA neurons or the potency of quinpirole to induce inhibition of these cells. However, 28-day SKF 38393 treatment (but not 14-day treatment) eliminated the ability of subsequent (24 h later) acute SKF 38393 to alter the rate-dependent nature of quinpirole-induced inhibition. In contrast, one week after a 28-day SKF 38393 treatment we found that quinpirole-induced inhibition by itself was no longer rate-dependent, an effect which was reversed by acute pretreatment with the D1 antagonist SCH 23390. This latter finding is suggestive of enhanced endogenous D1 tone. Similarly, 28-day SKF 38393 treatment eliminated the effect of subsequent acute SKF 38393 on sciatic nerve stimulation-induced inhibition of nigrostriatal DA neurons, whereas one week after the chronic D1 regimen these cells were highly sensitive to acute D1 enhancement of the response to sciatic nerve stimulation. In order to address the postsynaptic effects of chronic D1 stimulation, the influence of iontophoretically administered SKF 38393 was examined on type I caudate neurons. Again, 28-day SKF 38393 treatment resulted in reduced sensitivity of caudate neurons tested 24 h later, and an enhanced sensitivity was observed one week after the completion of chronic SKF 38393 administration. Thus, chronic SKF 38393 induced functional desensitization of D1 receptors, but one-week withdrawal was followed by sensitization.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗
PubMed1991

Supplemental corn grain for steers grazing native rangeland during summer.

Effects of supplemental corn grain on forage OM intake (FOMI), digesta kinetics, ruminal fermentation patterns, in vitro OM digestibility (IVOMD), and in situ OM digestion were examined in steers grazing summer blue grama rangeland in northeastern New Mexico during July and August 1988. Sixteen ruminally cannulated steers (average BW 507 kg) were allotted to four treatments and individually fed whole-shelled corn at 0, .2, .4, and .6% of BW in a complete random design with repeated measurements over time. Forage OMI decreased linearly (P = .02) with increasing levels of supplemental corn; however, a tendency toward greater FOMI, as well as faster particulate and fluid passage, was observed when corn was fed at .2% of BW compared with 0, .4, or .6% of BW. Molar proportions of butyrate increased (P less than .10) but molar proportions of acetate and propionate, ruminal pH, and total VFA concentration did not change (P greater than .10) with added corn. Added corn linearly decreased (P less than .10) ruminal ammonia N concentrations in July, but patterns were inconsistent in August. A cubic response (P less than .05) for in situ OM disappearance with added corn was noted after 24, 72, and 96 h of incubation. Supplemental whole corn fed at .2% of BW had no detrimental effects and tended to increase FOMI. However, supplemental corn fed at .4 or .6% of BW decreased FOMI compared with 0 or .2% of BW.

Ammonia↗
PubMed1990

The effects of the phencyclidine analogs BTCP and TCP on nigrostriatal dopamine neuronal activity.

Extracellular single unit recording techniques were used to evaluate the effects of two phencyclidine (PCP) derivatives. N-[1-(2-benzo(b)thiophenyl)cyclohexyl]piperidine (BTCP) and N-[1-(2-thiophenyl)cyclohexyl]piperidine (TCP) on the electrophysiological activity of antidromically identified nigrostriatal dopamine (DA) neurons in chloral hydrate-anesthetized rats. I.v. BTCP produced a dose-dependent decrease in the firing rate of identified nigrostriatal DA neurons whereas TCP elicited a dose-dependent biphasic effect which was characterized by an activation of cell firing at low doses followed by a reversal of the response with larger doses. A hemitransection of the brain anterior to the substantia nigra significantly reduced the inhibitory effect of BTCP while this surgical procedure did not affect the response to TCP. However, iontophoretic application of BTCP induced a current-dependent inhibition of the spontaneous activity of cells while local application of TCP had no effect on the firing rate of these cells. These data indicate that PCP analogs are able to interact with the nigrostriatal DAergic pathway through distinct and opposing mechanisms. The results are discussed in light of recent observations that BTCP is selective for the DA uptake site while TCP is selective for the high affinity PCP binding site.

Action Potentials↗
PubMed1990

Statistical analysis of dose-response curves in extracellular electrophysiological studies of single neurons.

The application of polynomial regression and the analysis of covariance (ANCOVA) to dose-response (DR) data derived from extracellular electrophysiological studies of midbrain dopamine neurons and noradrenergic locus coeruleus neurons in vivo is demonstrated and discussed. Third-order polynomial regression was found to be a better method for estimating ED50 values than probit analysis of linear regression. ANCOVA provides a more powerful statistical method than ANOVA for detecting significant differences in ED50 values or DR curves when a confounding variable such as basal discharge rate is present. The methods of analysis presented herein should be useful in the analysis of other types of neurons in electrophysiological studies.

Action Potentials↗
PubMed1990

Dopamine neuron ontogeny: electrophysiological studies.

The ontogeny of nigrostriatal dopamine (NSDA) neurons was examined with single-unit extracellular electrophysiological methods. The physiological and pharmacological characteristics of 2-, 4-, and 5-week-old rat pup NSDA neurons were compared with those of adults (8-10 weeks old). Although the basal discharge rate, conduction velocity, and firing pattern of NSDA neurons from 4- and 5-week-old rats were similar to adults, the 2-week-old-rats differed significantly in all three of these physiological characteristics. The conduction velocity and basal discharge rate were found to be significantly lower in the 2-week-old pups relative to adults. In addition, there were significantly fewer bursting NSDA neurons in 2-week-olds than there were in adults. Two and 4-week-olds exhibited significantly lower sensitivity to cumulative intravenous doses of apomorphine. In contrast, the sensitivity to cumulative intravenous doses of quinpirole was found to be similar across all age groups. It is evident that the pharmacological and physiological properties of NSDA neurons are in a dynamic state of flux during postnatal development. These electrophysiological findings are discussed in the context of the perinatal development of midbrain DA systems.

Action Potentials↗
PubMed1990

Effect of rotating monensin plus tylosin and lasalocid on performance, ruminal fermentation, and site and extent of digestion in feedlot cattle.

Two trials were conducted to evaluate the effects of ionophore rotation programs on performance and digestion by feedlot cattle. A 90% concentrate diet was fed with treatments of no ionophore (C), 33 mg lasalocid/kg diet daily (L), 29 mg monensin plus 11 mg tylosin/kg diet daily (MT), and daily (D) and weekly (W) rotation of L and MT. In Trial 1, feedlot performance of 200 crossbred steers (average initial BW 296 kg) was evaluated during a 133-d period. In Trial 2, four crossbred steers (average initial BW 376 kg) fitted with ruminal, duodenal and ileal cannulas were used in a 4 x 4 Latin square design to evaluate treatment effects (excluding W) on ruminal fermentation and site and extent of digestion. In Trial 1, daily rotation of L and MT improved (P less than .10) feed:gain ratio compared with other treatment groups, but daily feed intake did not differ (P greater than .10) among treatments. Daily gain was greater (P less than .10) for steers fed D than for those fed C or MT, but not different from that of steers fed L or W. Carcass measurements did not differ (P greater than .10) among treatments. In Trial 2, ruminal molar proportions of butyrate and valerate were decreased (P less than .07) by MT and D compared with C and L. Proportions of other VFA, ammonia concentrations and ruminal pH did not differ among treatments. Ionophore treatments did not affect site or extent of digestion of OM, starch or N; no differences among treatments were observed for efficiency of microbial protein synthesis. Although daily rotation of L and MT improved performance of growing-finishing feedlot steers, this improvement was not attributable to alterations in ruminal fermentation, or in site or extent of nutrient digestion.

Animals↗
PubMed1990

Serotonergic afferent regulation of the basic physiology and pharmacological responsiveness of nigrostriatal dopamine neurons.

The electrophysiological responsiveness of nigrostriatal dopamine (DA) neurons to dorsal raphe stimulation and to systemic administration of serotonin (5-HT) selective compounds was examined in chloral hydrate-anesthetized rats. Electrical stimulation of the dorsal raphe selectively inhibited the firing rate of slowly firing (less than 4 spikes/sec) DA neurons. The 5-HT-1A agonists 8-hydroxy-2-(di-n-propylamino)tetralin and 5-methoxy-N,N-dimethyltryptamine preferentially increased the firing rate of slowly firing DA neurons, but did not alter the responsiveness of these cells to quinpirole-induced inhibition of firing rate. This increase in firing rate was not observed following depletion of brain 5-HT by the neurotoxin 5,7-dihydroxytryptamine. The 5-HT-1B agonists trifluoromethylphenylpiperazine and M-chlorophenylpiperazine had only weak inhibitory effects on the firing rates of DA neurons, and also failed to alter the responsiveness of DA neurons to quinpirole-induced inhibition. Depletion of brain 5-HT (greater than 80%) by either para-chlorophenylalanine or 5,7-dihydroxytryptamine eliminated the rate-dependent nature of quinpirole-induced inhibition of nigrostriatal DA neurons, while having limited effects on the basal electrophysiological activity of these cells. These data suggest that 5-HT systems exert subtle influences on the activity and pharmacological responsiveness of nigrostriatal DA neurons.

Animals↗
PubMed1990

Effects of (+)-4-propyl-9-hydroxynaphthoxazine on midbrain dopamine neurons: an electrophysiological study.

(+)-4-Propyl-9-hydroxynaphthoxazine (PHNO) is a highly potent, D2-selective dopamine (DA) receptor agonist. In the present study, we have examined the electrophysiological effects of PHNO on identified nigrostriatal DA (NSDA), mesoaccumbens DA (MADA) and Type I caudate neurons. Intravenous PHNO dose-dependently inhibited the firing rate of NSDA and MADA neurons in both chloral hydrate (CH)-anesthetized rats (ED50 values = 21.2 +/- 1.2 and 26.5 +/- 1.4 ng/kg, respectively) and locally anesthetized, paralyzed rats (ED50 values = 105.0 +/- 1.4 and 109.1 +/- 1.4 ng/kg, respectively). PHNO was significantly more potent in the CH-anesthetized rats. There was a significant, positive correlation between basal firing rate and log ED50 for NSDA neurons in both preparations and for MADA cells only in CH-anesthetized animals. Neither pretreatment with the D1 receptor agonist SKF 38393 nor hemitransection of the forebrain altered the rate-dependent nature of PHNO-induced inhibition of NSDA neurons. Likewise, depletions of serotonin with either p-chlorophenylalanine or 5,7-dihydroxytryptamine failed to alter the rate-dependent PHNO-induced inhibition of NSDA neurons. Iontophoretically applied PHNO inhibited both NSDA and MADA neurons to a similar degree as either DA or the D2 agonist quinpirole. In contrast, the similar effects of PHNO and quinpirole on Type I caudate neurons were significantly different than those of DA. These results suggest that PHNO inhibits midbrain DA neurons via stimulation of somatodendritic autoreceptors and that PHNO exhibits an electrophysiological profile characteristic of D2 agonists. In contrast to quinpirole, however, the rate-dependent nature of PHNO-induced inhibition of these cells was resistant to modulation.

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

(+/-)-3,4-Methylenedioxymethamphetamine-induced changes in the basal activity and pharmacological responsiveness of nigrostriatal dopamine neurons.

The present study examined the effects of methylenedioxymethamphetamine (MDMA) on the basal activity and pharmacological responsiveness of rat nigrostriatal dopamine (DA) neurons. Under standard in vivo extracellular single-unit recording conditions, acute MDMA administered alone (i.v.) inhibited the firing rate of nigrostriatal DA neurons in a dose-dependent fashion. The potency of MDMA to elicit this inhibition was significantly reduced following depletion of either serotonin or DA. Acute MDMA pretreatments (10 mg/kg i.v., 90 s) also profoundly enhanced the sensitivity of nigrostriatal DA neurons to the rate-inhibitory effects of the D-2 DA receptor agonist quinpirole but not apomorphine. It has previously been demonstrated that the ability of quinpirole and apomorphine to inhibit nigrostriatal DA neuronal activity is dependent on the basal firing rate of the cell. Both acute MDMA and a single dose of MDMA (15 mg/kg i.p.) one week prior eliminated the rate dependency of quinpirole- and apomorphine-induced inhibition of the firing rate of these cells. These data suggest that, although MDMA is known to be a serotonergic neurotoxin, this compound may also exert direct functional effects on the nigrostriatal DA system.

3,4-Methylenedioxyamphetamine↗
PubMed1989

Repeated amphetamine: reduced dopamine neuronal responsiveness to apomorphine but not quinpirole.

Extracellular recordings from single nigrostriatal dopamine (DA) neurons in rats revealed significantly reduced neuronal sensitivity to the inhibitory effects of i.v. apomorphine following repeated amphetamine (4 mg/kg per day i.p., 14 days). This effect was reversed by acute SCH 23390. Quinpirole sensitivity was reduced in amphetamine-treated rats only following acute SKF 38393 pretreatment. These results suggest that, in amphetamine-treated animals, D-1 receptor activation is important for the expression of reduced nigrostriatal DA neuron sensitivity to apomorphine.

Amphetamine↗
PubMed1989

Chloral hydrate anesthesia alters the responsiveness of identified midbrain dopamine neurons to dopamine agonist administration.

Single-unit electrophysiological recording techniques were used to sample the basal activity of antidromically identified nigrostriatal and mesoaccumbens dopamine (NSDA and MADA, respectively) neurons and to examine the responsiveness of these cells to dopamine agonist-induced inhibition of cell firing rate in either chloral hydrate-anesthetized or paralyzed rats. Paralyzed rats exhibited a greater percentage of burst-firing cells (69%) than did anesthetized animals (37%). Furthermore, paralyzed rats were less sensitive to the mixed D1/D2 DA receptor agonist apomorphine and the selective D2 DA receptor agonist quinpirole. However, significantly higher doses of d-amphetamine were required in paralyzed animals only with respect to inhibiting MADA neurons. The abilities of apomorphine and quinpirole to inhibit NSDA cell firing were rate-dependent in both anesthetized and paralyzed rats, whereas d-amphetamine-induced inhibition was rate dependent only in anesthetized animals. In contrast, apomorphine- and quinpirole-induced inhibition of MADA neurons were rate-dependent only in anesthetized rats, whereas d-amphetamine-induced inhibition was rate-dependent only in paralyzed animals. These results suggest that general anesthesia exerts subtle effects on the basal activity and pharmacological responsiveness of midbrain dopamine neurons.

Action Potentials↗
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↗