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C D Blaha

Publications and source records attributed to C D Blaha.

At least 37 records · Page 2Linked to original sources
PubMed1996

Evaluation of stearate-graphite paste electrodes for chronic measurement of extracellular dopamine concentrations in the mammalian brain.

Chronoamperometric procedures, in combination with pharmacological treatments, were used to verify whether stearate-modified graphite paste recording electrodes (SGEs) could measure basal extracellular dopamine (DA) concentrations in the striatum of awake rats over a 3-week period of implantation. Baseline chronoamperometric signals were unaffected by systemic injections of ascorbate (AA) or the monoamine oxidase inhibitor pargyline, or by intraventricular infusions of the AA degrading enzyme AA-oxidase. In contrast, systemic injections of d-amphetamine or nomifensine increased, and gamma-butyrolactone decreased, the signal in a reproducible fashion over a similar test period. In addition, 6-hydroxydopamine lesions of the nigrostriatal DA pathway attenuated the ability of d-amphetamine to increase, and gamma-butyrolactone to decrease, the chronoamperometric signal. In separate studies, reverse microdialysis, performed with dialysis probes implanted directly adjacent to SGEs in the striatum, permitted the assessment of electrode selectivity, sensitivity, response linearity, and detection limits to DA. Perfusion of the probe with normal Ringer solution (5 microliters/min) decreased the baseline chronoamperometric signal by 10 nA. Comparable decreases in the baseline signal were observed after systemic injections of gamma-butyrolactone or medial forebrain bundle infusions of tetrodotoxin, suggesting these decreases reflected depletion of extracellular DA to levels below the electrode's detection limit. Reverse dialysis with high concentrations of AA, DOPAC, 5-HT, or 5-HIAA, failed to reverse the decrease in the chronoamperometric signal induced by dialysis. In contrast, reverse dialysis with a physiologically relevant range of DA concentrations, in rats pretreated with the DA uptake blocker nomifensine, increased the chronoamperometric signal in a linear fashion with a detection threshold of < 20 nM. Combined, these results indicate that the baseline chronoamperometric signals recorded at +0.20 V in the striatum with SGEs do not reflect changes in extracellular concentrations of AA, DA metabolites, or indoles, but rather represent neuronally mediated nanomolar changes in extracellular DA concentrations, even after extended periods of implantation in brain tissue.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1995

Correlation of striatal dopamine release and peripheral hypertension after transient ischemia in gerbils.

PURPOSE: Intracranial norepinephrine release has been associated with post-carotid endarterectomy hypertension in human beings. To study this phenomenon under more controlled conditions, we studied the relationship of cerebral catecholamines and blood pressure in gerbils, whose cerebral circulation is similar to that in human beings. METHODS: Twelve anesthetized gerbils underwent iliac artery blood pressure monitoring and in vivo electrochemistry catecholamine monitoring with use of catecholamine-specific electrodes placed stereotactically into the cerebral striatum. Six gerbils underwent 10 minutes of bilateral carotid artery occlusion (ischemic), whereas six underwent carotid artery dissection without occlusion (control). RESULTS: The control group demonstrated a continuous gradual decline in blood pressure and striatal catecholamine during the 150-minute observation period. In contrast the ischemic gerbils demonstrated a sharp catecholamine rise during ischemia, a marked catecholamine drop shortly after carotid artery unclamping, and then a secondary larger catecholamine release that peaks in 60 minutes and gradually returns to baseline in 120 minutes. The blood pressure closely followed the catecholamine levels, with a sharp 20 mm Hg rise in blood pressure above baseline during carotid artery occlusion, followed by a dramatic 10 mm Hg drop below baseline after carotid artery unclamping and then a gradual rise of the blood pressure 25 mm Hg above baseline, which peaks in 80 minutes, with a gradual decline to the same blood pressure as in the control subjects 120 minutes after ischemia. CONCLUSION: We conclude that striatal catecholamine release correlates with peripheral blood pressure during transient cerebral ischemia and reperfusion. This phenomenon may explain the mechanism of post-carotid endarterectomy hypertension in human beings, and this gerbil model can be used to study its prevention and treatment.

Animals↗
PubMed1993

Modulation of dopamine efflux in the striatum following cholinergic stimulation of the substantia nigra in intact and pedunculopontine tegmental nucleus-lesioned rats.

The effects of microinjections of cholinergic agents into the substantia nigra pars compacta on dopamine (DA) efflux in the anterior dorsomedial striatum of urethane-anesthetized rats were investigated using in vivo chronoamperometry and intracerebral microdialysis techniques. A dose-dependent augmentation of DA efflux as evidenced by increases in the chronoamperometric signals was observed in the striatum following nigral microinjections of the cholinergic agonists nicotine or carbachol. Enhancing extracellular concentrations of ACh in the substantia nigra by intranigral infusions of the cholinesterase inhibitor neostigmine also resulted in an increase in the chronoamperometric signal corresponding to DA overflow in the striatum. These stimulatory effects of neostigmine on DA efflux in the striatum were confirmed using in vivo microdialysis. Compared to sham-operated control animals, quinolinic acid lesions of the pedunculopontine tegmental nucleus (PPTg) resulted in an attenuation of the stimulatory effects of intranigral neostigmine on DA efflux in the striatum. In contrast, these treatments resulted in an enhancement of striatal DA efflux in response to nigral infusions of the direct ACh receptor agonist nicotine. Combined, these data suggest that PPTg cholinergic neurons are indirectly involved in regulating the activity of the striatum by modulating the activity of DA neurons in the substantia nigra of the rat.

Animals↗
PubMed1992

Extracellular dopamine in the rat striatum during ischemia and reperfusion as measured by in vivo electrochemistry and in vivo microdialysis.

The effects of transient global forebrain ischemia and reperfusion on striatal extracellular dopamine levels were analyzed using both in vivo electrochemistry and in vivo microdialysis in urethane-anesthetized rats. Electrochemical records showed that extracellular dopamine levels increased once during the period of ischemia, and a second time during reperfusion. This biphasic pattern was not detected by microdialysis, probably because of the relatively low time resolution of this technique. Microdialysis provided evidence that the voltammetric signal was a measure of dopamine, and also allowed measurement of the metabolites dihydroxyphenylacetic acid and homovanillic acid, both of which decreased during ischemia. The biphasic dopamine pattern seen in rats is similar to that reported previously in gerbils, suggesting that it is a phenomenon common to transient ischemia and reperfusion across different species and models of transient global ischemia. This phenomenon may have important implications for therapeutic intervention in cerebral ischemia.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1992

Pharmacological evidence for common mechanisms underlying the effects of neurotensin and neuroleptics on in vivo dopamine efflux in the rat nucleus accumbens.

The effects of the neuropeptide neurotensin and the typical neuroleptic haloperidol on dopamine efflux were compared in the posteromedial nucleus accumbens of the chloral hydrate-anesthetized rat using in vivo chronoamperometry. Both neurotensin and haloperidol administration elicited an immediate increase in dopamine efflux in the nucleus accumbens. Gamma-hydroxybutyric acid lactone, an agent known to block impulse flow in dopamine neurons, either prevented when given before neurotensin or reversed neurotensin-induced increases in accumbens dopamine efflux. Haloperidol-induced increases in accumbens dopamine efflux were similarly affected by gamma-hydroxybutyric acid lactone. The dopamine receptor agonist apomorphine reversed neurotensin- and haloperidol-induced increases in dopamine efflux. Amphetamine, administered during the peak dopamine stimulatory effects induced by neurotensin or haloperidol, resulted in increases above baseline which were significantly greater than the effects of amphetamine alone. These combined drug treatment effects on baseline dopamine efflux were additive, indicating that the effects of amphetamine were not potentiated by neurotensin or haloperidol pretreatments. These in vivo results suggest that neurotensin and haloperidol may augment dopamine efflux in the nucleus accumbens via common mechanisms of action which may involve activation of mesotelencephalic dopamine neuronal firing. The inability of neurotensin to block amphetamine-induced efflux in the nucleus accumbens further suggests that neurotensin blockade of amphetamine-elicited locomotor activity is mediated by an action of neurotensin postsynaptic to dopamine nerve terminals in the nucleus accumbens.

Animals↗
PubMed1992

Pituitary-adrenal and dopaminergic modulation of schedule-induced polydipsia: behavioral and neurochemical evidence.

Five experiments investigated in rats the effects of increasing or decreasing plasma corticosterone levels on schedule-induced polydipsia and dopamine efflux in the nucleus accumbens. The results indicate that the acquisition of schedule-induced polydipsia could be decreased by adrenalectomy, blockade of corticosterone synthesis, or administration of corticosterone. Performance of established schedule-induced polydipsia was also decreased by adrenalectomy. The effects of corticosterone administration on established schedule-induced polydipsia depended on the level of performance. High levels of drinking were enhanced by a high dose of corticosterone, whereas low rates of drinking were increased by a low dose. Similar injections of corticosterone also significantly increased dopamine efflux. The relative involvement of pituitary-adrenal activity and dopamine neurotransmission in the nucleus accumbens in the acquisition and performance of SIP is discussed and related to contemporary hypotheses of schedule-induced behavior.

Animals↗
PubMed1991

Biphasic striatal dopamine release during transient ischemia and reperfusion in gerbils.

To clarify the nature of ischemic striatal dopamine release during the earliest periods of neuronal injury, we used chronoamperometry to measure dopamine levels every 60 seconds during various durations of ischemia in 32 gerbils. Catecholamine-selective electrodes were implanted into the brains of anesthetized gerbils subjected to 2, 5, or 10 minutes of transient forebrain ischemia or permanent forebrain ischemia. Four control animals showed a stable chronoamperometric baseline. In the six gerbils subjected to permanent ischemia, dopamine release was rapid during early ischemia and slowed with time. The four animals subjected to 2 minutes of ischemia showed minimal dopamine release. The six gerbils subjected to 5 minutes of ischemia demonstrated a noticeable dopamine release during ischemia, and three of the six developed a massive secondary dopamine release during reperfusion. All six animals subjected to 10 minutes of ischemia demonstrated a similar biphasic dopamine release twice the size of that observed in the 5-minute group. Pretreatment with pargyline in six additional gerbils subjected to 10 minutes of ischemia failed to modify significantly this biphasic pattern of dopamine release. We conclude that dopamine release occurs very early during ischemia and that its magnitude correlates with the duration of an ischemia insult. Reperfusion is associated with an even larger striatal dopamine release. This previously unreported biphasic dopamine release phenomenon may have important clinical implications in the management of cerebral ischemia.

Animals↗
PubMed1990

Sexual behavior enhances central dopamine transmission in the male rat.

Central dopamine transmission was examined in the nucleus accumbens and striatum of sexually experienced male rats during mating behaviour using in vivo brain microdialysis. Dopamine release increased significantly in the nucleus accumbens when males were placed in a novel mating chamber and when a receptive female was introduced behind a screen partitioning this chamber. Subsequently, during copulation dopamine transmission increased sharply, this being followed by a gradual decrease after the female was removed. In contrast, striatal dopamine transmission increased significantly only during copulation. These data provide a neurochemical basis for the well-known interactions between dopaminergic drugs and male sexual behaviour and demonstrate the feasibility of using brain microdialysis to elucidate the neurochemical correlates of motivated behaviour.

Animals↗
PubMed1990

Application of in vivo electrochemistry to the measurement of changes in dopamine release during intracranial self-stimulation.

Stearate-modified graphite paste recording electrodes were acutely or chronically implanted into the nucleus accumbens along with bipolar stimulating electrodes in the ipsilateral ventral tegmental area (VTA). Chronoamperometry was used to monitor changes in electrochemical signals that may correspond to the oxidation of dopamine (DA) during experimenter-administered stimulation (EAS) and intracranial self-stimulation (ICS). Application of EAS to stimulating electrodes in the VTA produced increases in the electrochemical signal in both the anesthetized and conscious preparation. The magnitude of both effects increased as a function of current intensity. Initiation of ICS was also accompanied by an immediate increase in the electrochemical signal. Rate-intensity experiments revealed a corresponding increase in both the ICS rates and the electrochemical signal with successive increases or decreases in current intensity. In subsequent experiments, intraperitoneal injections of DA uptake blockers nomifensine and GBR-12909 produced significant increases in the amplitude of the chronoamperometric signal which corresponded to drug-induced increases in bar press rates. The noradrenergic uptake blocker desipramine had no significant effect on either ICS rates or oxidation current. These data indicate that ICS of the VTA may produce concurrent increases in DA neurotransmission in the nucleus accumbens. The pharmacological studies are consistent with a dopaminergic substrate of brain stimulation reward at electrode sites in the VTA.

Anesthesia↗
PubMed1990

Effects of neurotensin on dopamine release and metabolism in the rat striatum and nucleus accumbens: cross-validation using in vivo voltammetry and microdialysis.

The effects of the neuropeptide neurotensin on dopamine release and metabolism in the posteromedial nucleus accumbens and anterior dorsomedial striatum of the anesthetized rat were investigated using in vivo chronoamperometry and intracerebral microdialysis techniques. A dose-dependent augmentation of dopamine efflux as evidenced by increases in the chronoamperometric signal was observed in the nucleus accumbens following intracerebroventricular injections of neurotensin. However, neurotensin failed to alter extracellular concentrations of dopamine in the striatum. The selective effects of neurotensin on mesolimbic dopamine neurons were confirmed using in vivo microdialysis. These results demonstrate that neurotensin can selectively enhance the release and metabolism of dopamine in neurons projecting from the ventral tegmental area to the nucleus accumbens.

Animals↗
PubMed1988

Selective inhibition of mesolimbic dopamine release following chronic administration of clozapine: involvement of alpha 1-noradrenergic receptors demonstrated by in vivo voltammetry.

The release of dopamine (DA) in vivo was compared in the striatum and nucleus accumbens following chronic (21 day) administration of clozapine (CLOZ) and repeated coadministration of haloperidol (HAL) and the alpha 1-noradrenergic (NE) receptor antagonist prazosin. Treatment with HAL reduced basal DA release in both brain regions, whereas treatment with CLOZ decreased basal DA release only in the accumbens. Chronic coadministration of HAL and prazosin resulted in decreased DA release in accumbens but not striatum. These results suggest that the alpha 1-NE receptor blocking properties of CLOZ may, in part, mediate its differential actions on nigrostriatal and mesolimbic DA release, an effect which may in addition contribute to its paucity of extrapyramidal side effects.

Animals↗
PubMed1987

Chronic treatment with classical and atypical antipsychotic drugs differentially decreases dopamine release in striatum and nucleus accumbens in vivo.

In vivo electrochemical techniques were employed to demonstrate that repeated treatment with classical antipsychotic drugs reduced basal dopamine (DA) release in the striatum and nucleus accumbens, whereas repeated treatment with atypical antipsychotics decreased DA release only in accumbens. Administration of apomorphine temporarily reversed these decreases to values comparable to those measured in vehicle-treated controls. These results suggest that the delayed onset of antipsychotic efficacy and extrapyramidal side effects involve a decrease in DA release in mesolimbic and nigrostriatal DA terminal fields, respectively. The results further suggest that induction of depolarization block in DA neurons may be the mechanism underlying these effects.

Animals↗
PubMed1987

Acute thioridazine stimulates mesolimbic but not nigrostriatal dopamine release: demonstration by in vivo electrochemistry.

In vivo electrochemical techniques were employed to demonstrate that haloperidol and (+)-butaclamol increased the release of dopamine (DA) in the striatum and nucleus accumbens, whereas thioridazine stimulated DA release only in the accumbens. The stimulatory effect of thioridazine was reversed by gamma-butyrolactone. Given that gamma-butyrolactone inhibits DA neuronal activity, these data indicate that the regional selectivity of thioridazine on DA release is due to its ability to preferentially stimulate DA cell firing in the ventral tegmental (A10) area and suggest that its antipsychotic properties depend on its actions in the mesolimbic DA system.

4-Butyrolactone↗
PubMed1987

A functional separation of behavioral stereotypy based on naloxone-reversible effects of seryl enkephalinamide: comparison with morphine.

Amphetamine's stereotypic behavioral actions, produced by the stimulant at a moderate dose, were inhibited by the systemic administration of seryl enkephalinamide, D-Ser2-D-Ser5-enkephalinamide, (Wy 42,896). The classical sequelae of stimulatory behavioral events: sniffing, head bobbing, rearing and locomotor activity, were significantly inhibited by the seryl enkephalinamide. Subsequently, pretreatment with the opiate receptor antagonist, naloxone, significantly blocked the inhibitory effects of the seryl enkephalinamide on the stereotypic and locomotor components. Concomitantly, the behavioral stereotypic component, licking, a behavior usually produced by opiates and only high doses of amphetamine, was significantly induced by the seryl enkephalinamide. Pretreatment with naloxone on the stimulatory behavioral effect of licking, produced a significant inhibitory effect. The combination treatment, consisting of both the seryl enkephalinamide and the stimulant amphetamine, caused a naloxone-reversible synergistic effect. These data show that the seryl enkephalinamide, produced concomitant, naloxone-reversible, inhibitory and stimulatory behavioral stereotypic effects. These data are discussed within the context of current neuronal theories which might underly the observed dose-related continuum of behavioral stereotypies produced by morphine and amphetamine.

Amphetamine↗
PubMed1987

Reversal by cholecystokinin of apomorphine-induced inhibition of dopamine release in the nucleus accumbens of the rat.

In vivo electrochemical techniques were used to study the effects of the sulfated (CCK8-S) and unsulfated (CCK8-US) forms of cholecystokinin octapeptide on apomorphine-induced inhibition of dopamine (DA) release in the nucleus accumbens of the anesthetized rat. A dose-dependent inhibition of DA release was observed with intravenous (i.v.) injections of apomorphine. CCK8-S administered i.v. at the nadir of the apomorphine-induced inhibition of DA release produced a transient and dose-dependent increase followed by a prolonged decrease in DA release CCK8-US was ineffective in altering apomorphine's inhibitory effects on DA release. The CCK receptor antagonist proglumide injected i.v. 10 min after apomorphine administration had no effect on apomorphine-induced inhibition of DA release, but blocked the effects of CCK8-S on this inhibition. Given that apomorphine may inhibit DA release by a direct hyperpolarizing action on DA neurons, the observation that CCK8-S temporarily reverses apomorphine-induced effects and further inhibits DA release suggests that CCK8-S exerts its inhibitory effects via a process of depolarization block in DA neurons. These findings indicate that apomorphine and CCK8-S may inhibit DA release in vivo by opposite effects on DA cell membrane potentials and suggest that endogenously released CCK may serve to modulate mesolimbic DA neurotransmission.

Animals↗
PubMed1987

Cholecystokinin-induced inhibition of dopamine neurotransmission: comparison with chronic haloperidol treatment.

A dose-dependent inhibition of DA release was observed by in vivo electrochemical techniques after acute i.v. injections of CCK8-S (1.0-8.0 micrograms/kg). The threshold dose was 1.0 microgram/kg, and maximum inhibition of release (90%) was obtained with doses of 4 and 8 micrograms/kg. Injections of CCK8-US (4-20 micrograms/kg) had no effect on DA release. Repeated treatment with haloperidol (0.5 mg/kg s.c.) for 21 days produced a 47% inhibition of DA release in the nucleus accumbens. Apomorphine (50 micrograms/kg) reversed the inhibitory effects of both acute injections of CCK8-S and prolonged haloperidol treatment on DA release. In contrast, apomorphine (50 micrograms/kg) administered alone inhibited DA release, presumably via hyperpolarization of DA neurons. The attenuation of DA release by either an acute injection of CCK8-S or repeated treatment with haloperidol is attributed to the induction of depolarization block in mesolimbic DA neurons. These data may be indicative of antipsychotic properties of CCK8-S.

Animals↗