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R K Talmaciu

Publications and source records attributed to R K Talmaciu.

10 recordsLinked to original sources
PubMed1996

Comparative dopamine-acetylcholine interactions in the ventral and dorsal striatum of rabbit and rat brain.

The dopamine (DA)-acetylcholine (ACh) interactions were investigated in dorsal (nucleus caudate, NC) and ventral (olfactory tubercle, OT) striatal regions, of rats and rabbits. Both regions receive a dense dopaminergic innervation and have high ACh concentrations. Brain slices of NC and OT from both animal species were prelabeled with [3H]choline and superfused. In rat and rabbit OT and NC, higher ACh release per pulse was elicited by lower than higher stimulation frequencies; in addition, rabbit tissues released a greater fraction of tissue [3H]transmitter than rat tissues. Blockade of D2 DA-receptors with sulpiride (1 microM), did not modify ACh release in OT and NC of rats and rabbits; suggesting that the lower ACh release observed in rat tissues is not due to an inhibitory dopaminergic tone on cholinergic neurons. Apomorphine (APO), a D2 DA-receptor agonist, inhibited in a concentration-dependent manner the evoked release of ACh from rat and rabbit NC (maximal inhibition = 90%). In rabbit OT, maximal inhibition induced by APO was 49 +/- 2% and in the rat OT, it was 23 +/- 1%. Sulpiride antagonized APO-induced inhibition of ACh release from rat and rabbit NC; however, it failed to prevent APO-induced inhibition in rat OT, and in the rabbit OT reduced it from 47% to 20 +/- 5%. These results indicate differences in the wiring of DA and cholinergic neurons and terminals in dorsal and ventral striatal structures, as well as between rat and rabbit tissues. Cholinergic ventral striatal structures may not receive a direct DA input, and afferent cholinergic nerve terminals (rather than interneurons) predominate in the ventral striatum.

Acetylcholine↗
PubMed1996

Differential effects of muscarinic receptor agonists and phorbol ester on muscarinic and D2-dopamine release-modulatory receptors.

The interaction between an active phorbol ester, 4-beta-phobol-12,13-dibutyrate (PDBu), and muscarinic cholinergic receptor (MAChR) agonists on the electrically evoked neurotransmitter release was studied in the striatal and prefrontal cortex (PFC) of the rabbit. MAChR agonists (carbachol and oxotremorine), physostigmine and PDBu enhanced dopamine (DA) release from striatum and prefrontal cortex. Pretreatment with PDBu antagonized the increase in DA release produced by MAChR agonists (M1 receptors). Pretreatment with MAChR agonists and physostigmine also inhibited the action of PDBu on DA release. The inhibition of ACh release from the striatum induced by MAChR agonists (M2 receptors) and by apomorphine (D2-DA receptors) was antagonized by PDBu. MAChR agonists, however, did not antagonize the effects of the D2 agonist on ACh release. In the prefrontal cortex, PDBu produced greater facilitation of DA release than in the striatum, and MAChR agonists were less effective in inhibiting the effects of PDBu on DA release. This study suggests that the facilitation of DA release induced by the MAChR agonists and that induced by PDBu occur via a similar mechanism: stimulation of protein kinase C. PDBu induces a broad-spectrum loss of responsiveness to M1-MAChR and M2-MAChR and to D2-DA release-modulatory receptors, which is probably due to massive protein kinase C stimulation, signaling cell overstimulation. MAChR agonists, on the other hand, would stimulate the protein kinase C in close proximity to the M1 ACh receptor, facilitating DA release but failing to induce broad-spectrum desensitization.

Animals↗
PubMed1991

Carbachol-phorbol ester interactions at muscarinic receptors modulating dopamine release from rabbit striatal slices.

Both 4-beta-12,13-dibutyrate phorbol-ester (PDBu) (EC50% = 82 +/- 12 nM) and carbachol (EC50% = 2.3 +/- 0.3.5 microM) enhanced dopamine (DA) release from rabbit striatal slices. No additivity was observed when slices were treated simultaneously with 0.1 microM PDBu and 10 microM carbachol. Pretreatment with PDBu (0.01-0.1 microM) abolished carbachol-induced facilitation of DA release. Pretreatment with carbachol (3-100 microM) antagonized the enhancement in DA release produced by PDBu. The effect of carbachol was blocked by atropine (0.1 microM) and not by hexamethonium (10 microM). The effect of PDBu was not modified by the acetylcholine receptor (AChR) antagonists. If muscarinic (MAChR) MAChR were blocked by atropine (0.1 microM), pretreatment with carbachol failed to antagonize PDBu-induced facilitation of DA release. This is the first report to indicate that activation of M1-MAChR by an agonist prevents the effects of an active phorbol-ester. We suggest that activation of M1-MAChR enhances DA release possibly through activation of PKC.

Animals↗
PubMed1990

Is the release of dopamine from medial prefrontal cortex modulated by presynaptic receptors? Comparison with nigrostriatal and mesolimbic terminals.

Results obtained from our in vitro studies employing superfused slices obtained from three functionally different brain regions rich in DA axon terminals were discussed. Striking qualitative and quantitative similarities were found for the modulation of DA release from the nucleus caudate and the OT of the rabbit. However, the PFC DA terminals showed important differences from the nigrostriatal and mesolimbic DA terminals. Although release modulatory D2 DA autoreceptors could also be demonstrated in superfused slices of the PFC, our results suggest that the cortical nerve terminals may have a lower number of functional autoreceptors or a reduced efficiency of coupling between receptors and inhibition of release. Either possibility could explain (a) the poor inhibitory efficacy of the agonists, (b) the small facilitatory effect of the antagonists, (c) the disproportionate increase in transmitter overflow produced by neuronal uptake inhibitors, and (d) the lack of synergism between uptake inhibitors and DA antagonists. When the efficacy of the autoreceptor mechanisms was evaluated at stimulation frequencies comparable to the in vivo firing rates reported for each of the three neuronal groups, it was found that DA release from the striatum and the OT was tightly modulated by presynaptic D2 DA receptors; whereas release from PFC was not. We propose that the autoreceptor-mediated control of DA release from PFC may not function in vivo, even though modulation of release by presynaptic D2 DA receptors from PFC terminals could be demonstrated under specific experimental conditions in vitro. However, it is envisaged that if in vivo firing rate of the PFC DA neurons is reduced, the inhibitory actions of DA agonists on DA release may be regained. From these and other studies it is apparent that drug effects on autoreceptors are highly dependent on the rate and duration of stimulation applied to a specific neuronal group. We propose that the basal status of activity of a specific neuronal target could determine the type and magnitude of the effect produced by a therapeutic agent acting at release modulatory receptors. The neuronal activity (firing rate and pattern) may be affected by physiological status, disease, and by current or previous drug treatments. The mechanisms by which PFC DA terminals release a larger proportion of their storage pool compared to other mesotelencephalic DA terminals is unknown and may represent a compensatory mechanism to the continuous rapid firing rates at which these neurons are exposed in vivo.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1989

Phorbol esters and D2-dopamine receptors.

4-beta-Phorbol-12,13-dibutyrate (PDBu), a powerful activator of protein kinase C (PKC), enhanced dopamine (DA) release evoked by electrical stimulation (1 Hz, 2 min) from the striatum and the prefrontal cortex of the rabbit. However, acetylcholine (ACh) release from the striatum (1 Hz, 2 min), was only enhanced slightly by PDBu. The increase in DA release induced by PDBu was reduced markedly at higher frequencies of stimulation. Sulpiride (10 microM) alone, a D2 DA-receptor antagonist, or combined with nomifensine (3 microM), a neuronal-uptake inhibitor, did not prevent PDBu-induced facilitation of DA release from prefrontal cortex or striatum. The D2 DA agonists (LY-171555, bromocriptine and apomorphine) inhibited in a concentration-dependent manner the stimulation-evoked overflow of DA and ACh from the striatum, and of DA from the prefrontal cortex. Pretreatment with PDBu antagonized the inhibitory effect of the three agonists on DA and ACh release. A reduction both in Emax and IC50 was observed in PDBu-treated slices. Removal of endogenous DA by pretreatment with reserpine and alpha-methyl-p-tyrosine, failed to prevent PDBu-induced antagonism of apomorphine effects on ACh release, indicating that the antagonism of agonist effects was not due to higher synaptic levels of endogenous DA. The inactive enantiomer of PDBu, 4-alpha-12,13-dibutyrate did not enhance DA release and failed to modify the effects of D2 agonists on DA release.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetylcholine↗
PubMed1989

Differential effects of phorbol ester on prefrontal cortex and striatal dopamine terminals: dependence on rate and duration of stimulation.

Compared to the nigrostriatal dopamine (DA) neurons, the mesocortical DA neurons projecting to the prefrontal cortex (PFC) are able to sustain higher levels of release when driven at high stimulation frequencies. The effect of a well known activator of protein kinase C (PKC), 4-beta-phorbol-12, 13-dibutyrate (PDBu), were compared on PFC and striatal DA terminals. DA release was monitored from slices of the rabbit PFC and striatum obtained from the same animal. The PKC activator, PDBu (30-1000 nM) enhanced the stimulation-evoked release (SER) of DA from PFC and striatum. The magnitude of the facilitation of DA release produced by PDBu was much greater from the PFC than from the striatum. In the striatum, PDBu produced a bell-shaped dose-response curve, i.e., 0.03 and 1 microM PDBu enhanced SER of DA by 25%, whereas 0.1 and 0.3 microM PDBu enhanced DA release by 60 and 100%, respectively (1 Hz, 120 pulses). In the PFC, 0.03 microM enhanced the SER of DA by 70% and 1 microM by 250% (1 Hz, 120 pulses). In addition, in the PFC, PDBu enhance the basal release of DA (+65% at 1 microM); this effect was not seen in the striatum. The inactive isomer, 4-alpha-phorbol-12, 13-dibutyrate (0.03-1 microM) failed to increase the SER and the basal release of DA from PFC or striatum. The SER of DA was dependent on the rate and duration of stimulation. However, under all conditions of stimulation studied DA release from PFC was always greater than from the striatum.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1988

Sustained high release at rapid stimulation rates and reduced functional autoreceptors characterize prefrontal cortex dopamine terminals.

The release of dopamine (DA) from mesocortical and nigrostriatal nerve terminal fields, as well as its modulation by auto- and heteroreceptors was investigated. Rabbit brain slices obtained from medial prefrontal cortex (PFC) and nucleus caudate (striatum) were prelabeled with [3H]DA in the presence of 0.3 microM desipramine. Neuronal depolarization was elicited by electrical stimulation. Higher stimulation-evoked overflow of [3H]DA (release) was observed from PFC than from striatal slices. At 0.3 Hz (120 pulses) release from the PFC was 60% higher than from the striatum, and at higher frequencies (10 Hz and 120 or 1200 pulses) the fraction of tissue radioactivity released from the PFC was 550% greater than that released from the striatum. These differences were not eliminated by blockade of autoreceptors with haloperidol, or by inhibition of neuronal uptake with nomifensine. These results suggest that the coupling between neuronal depolarization and DA release is more efficient in the PFC than in the striatum. This may allow the PFC terminals to sustain neurotransmission under continuous fast firing. Selective D2 agonists, as well as nonselective DA agonists, inhibited DA release in a concentration-dependent fashion from the PFC and the striatum. Their effects were blocked by l-sulpiride or haloperidol. SKF 38393, a selective D1 agonist, produced a small facilitation of release from both regions; its effects were blocked by SCH 23390 (a selective D1 antagonist). The latter was ineffective on its own. The maximal degree of inhibition of release produced by apomorphine, bromocriptine and LY-171555 was lower in the PFC than in the striatum; these differences were accentuated greatly at high stimulation rates. When the slices were stimulated at frequencies comparable to the "in vivo" firing rates for each neuronal group, apomorphine and LY-171555 were much weaker in inhibiting DA release from the PFC (10 Hz) than from the striatum (3 Hz). In the striatum, strong modulation of DA release by endogenous DA was observed; whereas little modulation was seen in the PFC. Nomifensine produced larger increases in the stimulation-evoked overflow of DA from PFC and there was no synergistic interaction between nomifensine and haloperidol in this structure. In the striatum, marked facilitation of DA overflow was observed when nomifensine and haloperidol were given together. Furthermore, haloperidol per se facilitated DA release from both brain regions; however, the degree of facilitation was frequency dependent in the striatum, but not in the PFC.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1986

Dopamine autoreceptors modulate dopamine release from the prefrontal cortex.

Electrical stimulation (at 0.3, 1, or 10 Hz, 120 pulses each) produced a calcium-dependent overflow of radioactivity from slices of the rabbit prefrontal cortex preloaded with [3H]3,4-dihydroxyphenylethylamine ([3H]DA, [3H]dopamine) in the presence of desipramine. Flat frequency-release curves were observed. Apomorphine and LY-171555 inhibited in a concentration-dependent fashion the evoked overflow of DA, an effect antagonized by haloperidol. Stimulation frequencies comparable to normal firing rates of mesocortical neurons (10 Hz) drastically reduced apomorphine-induced inhibition of DA overflow. Haloperidol produced greater facilitation of DA overflow at 10 than at 1 Hz. Nomifensine, a neuronal uptake inhibitor, enhanced DA overflow. These results indicate that mesocortical DA neurons projecting to the prefrontal cortex have release modulatory autoreceptors of the D2 subtype.

Animals↗
PubMed1986

Interactions between endogenous dopamine and dopamine agonists at release modulatory receptors: multiple effects of neuronal uptake inhibitors on transmitter release.

The authors investigated the mechanisms by which inhibitors of the neuronal uptake (NUI) of dopamine (DA) and prolonged stimulations at high rates antagonize the inhibition of acetylcholine (ACh) release from rabbit striatal slices produced by DA receptor agonists. Nomifensine (1 microM) reduced the potency and efficacy of apomorphine (APO) in inhibiting the evoked release of ACh (0.3 Hz, 39 pulses) (noncompetitive kinetics). Highest inhibitory potency and efficacy of APO were obtained at 0.3 Hz and 39 pulses. Increases in stimulation rates and number of pulses (3 Hz and 120 pulses) reduced APO potency and efficacy for inhibition of ACh release (noncompetitive kinetics). At 10 Hz and 500 pulses APO efficacy was further reduced, and the APO concentration-effect curve was biphasic. Inhibition of DA and ACh release produced by other DA receptors agonists such as bromocriptine, piribedil and LY-171555 was also reduced by prolonged stimulations at high frequencies. Depletion of endogenous DA stores by reserpine pretreatment abolished the antagonism of APO produced by NUI and reduced considerably the antagonism produced by high pulses and high rates of stimulation of APO- and LY-171555-induced inhibition of ACh release. However, even after combined pretreatment with reserpine and alpha-methylparatyrosine, the potency and efficacy of APO in inhibiting ACh release at 10 Hz and 500 pulses were less than the values obtained in 0.3 Hz and 39 pulses and at 3 Hz and 120 pulses. The biphasic nature of the APO concentration-effect curve at 10 Hz and 500 pulses was no longer present after reserpine. Interestingly, reserpine pretreatment failed to modify APO-induced inhibition of ACh release at 0.3 Hz and 39 pulses, suggesting that the sensitivity of the DA release modulatory receptors was not affected by the pretreatment. These results indicate that the high synaptic concentration of DA achieved at low stimulation rates in the presence of NUI and at high stimulation rates reduces the potency and efficacy of DA agonists in inhibiting ACh release. However, for prolonged stimulations at high rates not all of the changes seen with DA agonists are mediated by endogenous DA. At high concentrations (10 microM), cocaine and nomifensine inhibited the evoked release of ACh even after depletion of tissue DA stores by reserpine in the absence or presence of a alpha-methylparatyrosine.(ABSTRACT TRUNCATED AT 400 WORDS)

Acetylcholine↗