PubMed Health⌕ Search

Biomedical subjects

D A Bergstrom

Publications and source records attributed to D A Bergstrom.

36 records · Page 2Linked to original sources
PubMed1988

Acute reduction of dopamine levels alters responses of basal ganglia neurons to selective D-1 and D-2 dopamine receptor stimulation.

Extracellular single unit recording techniques were used to investigate dopamine agonist-induced changes in the tonic activity of globus pallidus neurons in normal control rats, and in rats in which dopamine levels were acutely reduced by alpha-methyl-para-tyrosine (AMPT) pretreatment. Systemic administration of the nonselective D-1/D-2 agonist apomorphine consistently induced large increases in the firing rates of globus pallidus neurons, as shown previously. The D-1 agonist SKF 38393 frequently induced no change in pallidal cell firing rates with doses up to 20 mg/kg; however, firing rates of 40% of the cells were stimulated by more than 20% of baseline and 14% were partially inhibited after 20 mg/kg SKF 38393. Following AMPT pretreatment, SKF 38393 induced only increases and no changes in activity; no decreases were observed. The D-2 agonist quinpirole typically increased pallidal neuron activity in a dose-dependent manner but was markedly less effective at stimulating pallidal neuron activity than apomorphine. In AMPT-treated rats, quinpirole's effects were significantly attenuated. Consistent with previous results, most cells showed large rate increases when SKF 38393 and quinpirole were coadministered to normal rats; these increases were similar in magnitude to those induced by apomorphine. In contrast to the observation that AMPT treatment altered the responses of globus pallidus neurons to individually administered quinpirole and SKF 38393, neither the increases in pallidal cell activity induced by apomorphine nor those induced by coadministration of SKF 38393 and quinpirole were significantly attenuated in AMPT-treated rats. The results support the idea that stimulation of both D-1 and D-2 receptors appears to be required to induce apomorphine-like changes in basal ganglia output. Moreover, the effects of individually administered D-1 and D-2 agonists observed in normal rats appear to depend upon the degree to which the complementary receptor subtype is stimulated by endogenous dopamine.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗
PubMed1987

D1 dopamine receptor activation required for postsynaptic expression of D2 agonist effects.

D1 and D2 dopamine receptors exert synergistic effects on the firing rates of basal ganglia neurons and on the expression of stereotyped behavior in rats. Moreover, the ability of D2 agonists to induce changes in basal ganglia single unit activity and spontaneous motor activity is dependent upon the presence of endogenous dopamine to stimulate D1 receptors; in rats treated with alpha-methyl-rho-tyrosine to reduce endogenous dopamine levels, the neurophysiological and behavioral effects of the D2 agonist quinpirole are significantly attenuated, while the effects of nonselective agonists like apomorphine, which stimulate both D1 and D2 receptors, or combinations of a D2 agonist and a D1 agonist are not attenuated. Thus, the previously held view that D2 receptors alone are responsible for evoking the changes in behavior and basal ganglia output induced by nonselective dopamine agonists and endogenous dopamine is not supported by these results, which indicate that these phenomena require concurrent stimulation of both dopamine receptor subtypes.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗
PubMed1987

Stimulation of both D1 and D2 dopamine receptors appears necessary for full expression of postsynaptic effects of dopamine agonists: a neurophysiological study.

The abilities of 4 dopamine agonists to inhibit the tonic single unit activity of substantia nigra dopamine neurons and stimulate tonic activity of globus pallidus neurons were compared to study the agonists' effects on pre- and postsynaptic dopamine receptors, respectively. The agonists studied were apomorphine and pergolide, which interact with both D1 and D2 receptors, and the selective D2 agonists quinpirole and RU 24926. Drugs were administered systemically. The 4 dopamine agonists were equipotent and equiefficacious at inhibiting the firing rates of dopamine neurons. In contrast, their effects on pallidal cells were not identical; apomorphine and pergolide induced significantly greater increases in pallidal cell activity than did quinpirole and RU 24926. In addition, pretreatment with a small dose of quinpirole did not attenuate the excitatory effect of apomorphine on globus pallidus cell activity, as low doses of apomorphine have previously been shown to do. Possible mechanisms underlying the differences in efficacy between the non-selective and D2 selective dopamine agonists in the globus pallidus were investigated. Coadministering quinpirole with apomorphine did not significantly attenuate the effect of apomorphine, suggesting that quinpirole is not a partial agonist at postsynaptic dopamine receptors. In addition, prazosin pretreatment did not attenuate the stimulatory effect of pergolide on firing rates of pallidal cells, indicating that the greater efficacy of the non-selective agonists was not due to concurrent stimulation of alpha 1 adrenergic receptors and dopamine receptors. However, the effect of quinpirole on pallidal cell activity was significantly potentiated by pretreatment with the D1 agonist RS-SKF 38393 but not its inactive enantiomer S-SKF 38393. These results suggest that concurrent D1 and D2 receptor stimulation may be necessary for the full expression of postsynaptic receptor-mediated effects of dopamine and dopamine agonists in the basal ganglia.

Adrenergic beta-Antagonists↗
PubMed1987

Neurophysiological investigation of effects of the D-1 agonist SKF 38393 on tonic activity of substantia nigra dopamine neurons.

The effects of the D-1 agonist SKF 38393 on tonic activity of rat substantia nigra pars compacta dopamine neurons were studied using extracellular, single-unit recording techniques. Unlike nonselective D-1/D-2 dopamine agonists or the D-2 agonist quinpirole, SKF 38393 did not inhibit dopamine neuronal activity when applied iontophoretically or when administered intravenously in doses up to 20 mg/kg to chloral hydrate-anesthetized rats. Moreover, pretreatment with SKF 38393 did not alter the inhibitory response of these neurons to apomorphine or the D-2 agonist quinpirole. However, in locally anesthetized, gallamine-treated, artificially respired rats, dopamine cell activity was significantly altered by i.v. administration of SKF 38393; firing rate increases and decreases were observed. Administration of the inactive enantiomer of SKF 38393, S-SKF 38393, did not induce similar changes in parallel experiments. These results support the idea that unlike D-2 autoreceptor stimulation, D-1 receptor stimulation does not exert a direct local effect on dopamine neurons in the substantia nigra pars compacta and suggest that D-1 receptor stimulation at sites postsynaptic to the dopamine cells may indirectly affect the activity of some dopamine neurons through long-loop feedback mechanisms.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗
PubMed1986

Differential electrophysiological effects of 3-PPP and its enantiomers on dopamine autoreceptors and postsynaptic receptors.

The activities of substantia nigra pars compacta dopamine and globus pallidus neurons have been examined following the systemic administration of ( +/- )-3-PPP and the enantiomers of 3-PPP to investigate the relative effects of these putative dopamine agonists on dopamine autoreceptors and postsynaptic dopamine receptors. ( +/- )-3-PPP inhibited the firing rates of 7 out of 10 dopamine cells completely (ED50 = 0.18 +/- 0.06 mg/kg) but caused no consistent or significant alterations in the firing rates of globus pallidus neurons, exhibiting an apparent selectivity for the dopamine D-2 autoreceptors. However, (+)-3-PPP effectively inhibited the activity of all dopamine neurons studied (ED50 = 0.09 +/- 0.03 mg/kg) and, like d-amphetamine, apomorphine and other dopamine agonists, significantly stimulated pallidal activity. (-)-3-PPP was less effective at inhibiting dopamine cell activity; it had no effect on firing rates of pallidal cells when given alone, but it reversed the pallidal rate increases induced by (+)-3-PPP and also blocked the rate increases induced by systemically administered apomorphine. The results show that (-)-3-PPP, given systemically, acts as a partial agonist in the substantia nigra pars compacta and as an antagonist on postsynaptic dopamine receptors. These effects of (-)-3-PPP appear to account for the apparent dopamine autoreceptor selectivity demonstrated by racemic 3-PPP and further indicate that the autoreceptors and postsynaptic dopamine receptors may be differentially affected by a drug with mixed agonist/antagonist properties. These conclusions are consistent with those obtained from other techniques and support the idea that the effects of dopamine agonists on the activity of dopamine neurons and globus pallidus cells can provide an indication of the relative selectivity of these drugs for pre- or postsynaptic dopamine receptors.

Action Potentials↗
PubMed1986

Neurophysiological evidence that D-1 dopamine receptor blockade attenuates postsynaptic but not autoreceptor-mediated effects of dopamine agonists.

The putatively selective D-1 dopamine receptor antagonist SCH 23390 was used to study the role of the D-1 dopamine receptor in mediating the pre- and postsynaptic effects of dopamine agonists in the basal ganglia. SCH 23390 (1 mg/kg) had no significant effect on the tonic activity of substantia nigra dopamine neurons in 47% of the 19 cells studied, while the firing rates of 53% of the cells were increased. SCH 23390 did not shift the dose response of these cells to apomorphine, whereas the selective D-2 antagonist, YM-09151-2 completely blocked apomorphine's inhibitory effects on nigral dopamine cell activity. These results suggest that SCH 23390 does not interact with the D-2 dopamine autoreceptors, but does excite a subpopulation of dopamine neurons presumably through postsynaptic actions. In contrast to its inability to modify the effects of apomorphine on dopamine autoreceptors, SCH 23390 partially to fully reversed the effects of apomorphine on globus pallidus and substantia nigra pars reticulata cell activity and significantly attenuated the effects of apomorphine, pergolide, quinpirole (LY 171555) and d-amphetamine on firing rates of globus pallidus neurons. The D-1 antagonist alone had no significant effect on tonic globus pallidus neuronal activity. SCH 23390 was more potent than haloperidol in its ability to attenuate the effects of apomorphine on pallidal activity, but unlike haloperidol, was unable to totally inhibit these effects, suggesting that the two antagonists block the excitatory effects of apomorphine on pallidal cell firing rates by different mechanisms. The serotonin2 receptor antagonist, ketanserin, had no effect on pallidal or dopamine cell activity, indicating that the effects of SCH 23390 were not mediated through interactions with serotonin2 receptors. These results suggest that D-1 receptor blockade attenuates the postsynaptic, but not autoreceptor-mediated effects of dopamine agonists.

Animals↗
PubMed1984

Dopamine attenuates the effects of GABA on single unit activity in the globus pallidus.

Studies were conducted to assess whether stimulation of dopamine receptors located in the globus pallidus might play a role in mediating the enhanced pallidal activity seen after systemic administration of dopamine agonists or D-amphetamine. Dopamine, applied iontophoretically, had modest effects on the activity of pallidal neurons; the baseline firing rates of 32% of cells recorded increased by an average of 23 +/- 2%, 18% decreased in rate and the remaining cells showed no significant rate change. More significantly, dopamine consistently attenuated the inhibitory actions of gamma-aminobutyric acid (GABA) in the globus pallidus. When dopamine was simultaneously iontophoresed with GABA, GABA's effectiveness at inhibiting pallidal activity was reduced by an average of 50%. Norepinephrine or acetylcholine, applied iontophoretically at equimolar concentrations and ejected at the same current as dopamine, caused no consistent attenuation of pallidal responses to GABA's rate effects. To determine whether the attenuation of GABA's inhibitory action by iontophoresed dopamine could be mimicked by systemic drug administration, apomorphine, 80 micrograms/kg, or D-amphetamine, 0.8 mg/kg, was given i.v. while GABA was iontophoresed. Apomorphine markedly decreased pallidal responses to the inhibitory effects of GABA in 75% of the cells by an average of 50%; haloperidol reversed this effect. Modulatory interactions between GABA and D-amphetamine were also observed in 5 of the 11 pallidal cells tested; GABA's inhibitory effect on pallidal cell activity was reduced by an average of 66% on these neurons. These results suggest that one way in which dopamine and dopamine agonists may affect basal ganglia function is by modulating GABAergic transmission in the globus pallidus.

Acetylcholine↗
PubMed1984

Dopamine agonists increase pallidal unit activity: attenuation by agonist pretreatment and anesthesia.

Intravenous administration of a single bolus dose of 1 mumol/kg of the dopamine agonists, pergolide and lisuride, caused marked increases in the unit activity of globus pallidus neurons in awake, paralyzed, locally anesthesized and artificially respired rats. These agonist effects were similar to those observed after administration of 1 mumol/kg apomorphine to awake, paralyzed rats; in rats anesthetized with chloral hydrate, however, responses to apomorphine were markedly attenuated. Subsequent administration of haloperidol reversed the effects of pergolide and pretreatment with haloperidol blocked the effects of lisuride. LSD (1 mumol/kg i.v.) did not effectively stimulate pallidal neuronal activity, suggesting that the ability to stimulate pallidal firing rates correlates better with dopamine, as opposed to serotonin, agonist potency. The ability of a non-excitatory dose of apomorphine to attenuate responses of pallidal neurons to a normally excitatory 1 mumol/kg dose of this agonist administered subsequently, was reconfirmed. Pretreatment with this 'priming' dose of apomorphine also attenuated the rate increases produced by d-amphetamine (8.7 mumol/kg) and enhanced the rate inhibitory effects of haloperidol. The 'priming' effect appears related to the dopamimetic effects of apomorphine; a non-excitatory dose of a second dopamine agonist, lisuride (0.07 mumol/kg i.v.), similarly blocked the effect of excitatory doses of lisuride (1 mumol/kg i.v.) on pallidal activity.

Action Potentials↗
PubMed1983

Electroconvulsive shock: effects on biochemical correlates of neurotransmitter receptors in rat brain.

The effects of electroconvulsive shock on neurotransmitter receptor binding sites in rat brain have been studied. Electroconvulsive shock decreased beta-adrenergic receptor binding sites in the cerebral cortex and hippocampus but not in the striatum, hypothalamus or cerebellum. The decrease in beta-adrenergic receptor binding sites was highly selective and was similar to the decrease in these receptors seen after chronic treatment of rats with tricyclic antidepressant drugs. Electroconvulsive shock selectively increased serotonin-2 receptor binding sites in the cerebral cortex. This effect was opposite to that of antidepressant drugs.

Animals↗
PubMed1982

Apomorphine increases the activity of rat globus pallidus neurons.

Systemic administration of apomorphine, 0.08-1.0 mg/kg, caused a haloperidol-reversible increase in the unit activity of spontaneously firing neurons in the rat globus pallidus. Low doses of apomorphine (50, 20 micrograms/kg), which are thought to produce a net decrease in the stimulation of postsynaptic dopamine receptors, did not cause effects opposite to those observed with larger doses in 96% of the cells monitored. Blockade of dopamine receptors by administration of haloperidol did cause a moderate reduction in neuronal activity but only after administration of fairly high doses.

Animals↗
PubMed1982

Time schedule of apomorphine administration determines the degree of globus pallidus excitation.

Intravenous administration of a single 320 microgram/kg bolus dose of apomorphine significantly increased in unit activity of rat globus pallidus neurons. Significantly attenuated responses to apomorphine were observed when 320 microgram/kg apomorphine was administered i.v. in divided doses (5, 35, 280 microgram/kg) 3-5 min apart or when 320 microgram/kg apomorphine was given i.v. 8 min after a nonexcitatory 'priming' dose (20 microgram/kg i.v.) of apomorphine. These results suggest that the expression and magnitude of apomorphine-induced excitation of pallidal neurons is influenced by the time schedule of drug administration.

Animals↗
PubMed1981

Electroconvulsive shock and reserpine: effects on beta-adrenergic receptors in rat brain.

Electroconvulsive shock (ECS) administered once daily for up to 14 days decreases beta-adrenergic receptor binding in the cortex and hippocampus in a time-dependent manner. The decrease in binding in the cortex lasts at least 1 week after the last shock. In the striatum, hypothalamus, or cerebellum, 14 days of ECS did not produce significant changes in beta-adrenergic receptor binding. The brain regional pattern of beta-adrenergic receptor changes suggests that repeated ECS affects beta 1-adrenergic receptors in brain regions that receive a noradrenergic innervation activated by ECS. The effects of ECS on neurotransmitter receptor binding appear to be highly selective. Of five receptors in the cortex and three receptors in the hippocampus measured, only beta-adrenergic receptor binding is decreased. Chronic footshock stress does not alter beta-adrenergic receptor binding sites in the cortex, indicating that the effects of ECS are not due to stress alone. The effects of ECS on reserpine-induced alterations in beta-adrenergic receptor binding sites were also examined. Ten days of ECS following chronic reserpine injections reverses the increased binding of beta-adrenergic receptors.

Animals↗
PubMed1981

Neuronal responses of the globus pallidus to systemic administration of d-amphetamine: investigation of the involvement of dopamine, norepinephrine, and serotonin.

Systemic administration of d-amphetamine (d-AMP) caused significant increases in the unit activity of spontaneously firing neurons in the rat globus pallidus. Intravenous injection of 0.2 mg/kg of d-AMP produced an average increase of 32% while a cumulative dose of 6.4 mg/kg of d-AMP increased cell firing 81% above base line control. The excitatory effects of d-AMP on pallidal cells were effectively blocked and reversed by haloperidol. Increasing intravenous doses of l-amphetamine (l-AMP), totaling 12.8 mg/kg, caused a slight excitation of pallidal neurons. The average maximum increase was 18.3%. Minor rate-elevating effects were also observed after systemic administration of desmethylimipramine and clonidine. The serotonin uptake inhibitor, fluoxetine, produced varied changes in firing frequencies. Pretreatment with reserpine and alpha-methyl-p-tyrosine significantly attenuated the d-AMP-induced increase in pallidal activity. These results suggest that dopamine plays a prominent role in mediating the stimulatory effects of d-AMP on the firing rates of a population of globus pallidus cells in gallamine-paralyzed rats.

Animals↗
PubMed1981

Single unit responses of substantia nigra and globus pallidus neurons to GABA agonist and antagonist drugs.

The studies reported here shed some new light upon the role of GABA within the basal ganglia. Although the proposed inhibitory interaction between the striatonigral GABA pathway and nigral dopamine neurons has, over the years, received the greatest attention, it now appears that this interaction may constitute only one part of a more extensive and perhaps more physiologically significant network of GABA-mediated effects upon populations of non-dopaminergic neurons. Specifically, evidence has been presented which indicates that the substantia nigra pars reticulata and the globus pallidus, two regions known to receive striatal GABAergic fibers, each contain groups of cells with a more marked ability to be affected by GABA and GABAmimetic drugs than the nigrostriatal dopamine neurons. Since reticulata and pallidal neurons seem at least as likely as dopamine neurons to be targets of this striatal GABAergic pathway, a much more expanded role for GABA within the basal ganglia might now be explored. Given their marked sensitivities to GABA, if reticulata and pallidal cells do lie postsynaptic to GABA terminals then function in several motor-related areas to which these cells project might be greatly affected by striatal and pallidal GABAergic efferents. Future studies aimed at elucidating the nature and importance of these GABA-mediated interactions may ultimately provide new clues about how the basal ganglia influence motor function.

Animals↗
PubMed1979

Adrenergic and serotonergic receptor binding in rat brain after chronic desmethylimipramine treatment.

The effects of chronic administration of the tricyclic antidepressant agent desmethylimipramine (DMI) on brain adrenergic and serotonergic receptor binding processes were studied. We examined the kinetic properties of alpha adrenergic, beta adrenergic and serotonergic receptor binding sites in cortical and subcortical brain regions of rats treated chronically for various time periods with DMI(6 mg/kg i.p. daily). After 1 week of daily injections, beta receptor binding density in the cortex was significantly decreased. The reduced density of the cortical beta receptors was evident throughout a 12-week administration period. It was not until after 6 weeks of DMI administration that a significant reduction in the subcortical beta receptors was evident. Compared to saline-injected controls, chronic DMI administration lowered [3H]dihydroalprenolol binding in the hippocampus but not in the striatum. After 12 weeks of DMI we detected no differences in alpha adrenergic binding characteristics in the cortex or subcortical forebrain using [3H]dihydroergocryptine as the binding ligand. There was no consistent alteration in the cortical serotonin receptor densities throughout the 12 weeks of DMI administration, and DMI had no effect on the serotonergic binding characteristics in the subcortical forebrain region. We conclude that chronic DMI administration selectively decreases the density of beta adrenergic receptors in rat brain.

Animals↗