Biomedical subjects

B C Sun

Publications and source records attributed to B C Sun.

At least 37 records · Page 2Linked to original sources

PubMed1993

Repeated reserpine treatment alters firing pattern and responses of substantia nigral dopamine neurons.

Repeated reserpine treatment (1 mg/kg x 6 days) increased the number of spontaneously active substantia nigra pars compacta (SNC) dopamine (DA) cells and altered the firing pattern to a more irregular one in locally anesthetized rats. The selective DA D1 receptor agonist, SKF 38393, although having little effect on SNC DA cells in normal rats, profoundly inhibited the firing rate of SNC DA cells in reserpinized rats. On the contrary, the DA D2 receptor agonist, N-0437, significantly inhibited the firing rate of SNC DA cells in control rats, however, the inhibition was not significantly altered by reserpine. The inhibitory effect of the mixed DA receptor agonist, apomorphine, was significantly enhanced after reserpine treatment. In addition, the inhibition of SNC DA cell firing produced by D1 and D2 receptor agonists in reserpinized rats was reversed only by their own subtype antagonists. These results suggest that repeated reserpine treatment renders SNC DA cells responsive to D1 receptor stimulation, and that D1 receptors play a more important role than D2 receptors in the supersensitivity of SNC DA cells induced by repeated reserpine treatment. The results also indicate that D1 and D2 receptor agonists inhibit SNC DA cell firing separately and synergically in reserpinized rats.

Animals↗

PubMed1992

Dual actions of (-)-stepholidine on dopamine receptor subtypes after substantia nigra lesion.

1. It was found that the contralateral rotation challenged by (-)-SPD (4 mg/kg, ip) in 6-OHDA-lesioned rats had a gradually progressive process with long latent period and a maximal response on 63 days after lesion. This steady contralateral rotation was preferably antagonized by D-1 antagonist SCH23390 than D-2 antagonists. During its latent period (-)-SPD exhibited the antagonistic effect to APO, while during its period of full response (-)-SPD could potentiate the APO-induced rotation. 2. In the rats lesioned with kainic acid plus 6-OHDA to destroy the SNC and SNR, (-)-SPD and SKF-38393 challenged neither contralateral nor ipsilateral rotation, while APO still induced the rotation but towards ipsilateral side, just opposite to that in 6-OHDA-lesioned rats. In this case, (-)-SPD antagonized the response to APO as did SCH 23390. 3. These evidences suggest that the agonistic action of (-)-SPD is resulted from D-1 receptor subtype at the SNR under supersensitive functional state. The fact that SNR lesion could completely eliminate the agonistic action of (-)-SPD further indicate that the D-1 receptors in the ipsilateral SNR may be the sites of action of (-)-SPD. The dual actions of (-)-SPD are dependent upon the supersensitivity of D-1 receptor subtypes which render the antagonistic action to convert into the agonistic.

Animals↗

PubMed1992

Effects of (-)-stepholidine on firing activity of dopamine neurons in ventral tegmental area of rats.

Extracellular single-unit recording techniques were used to evaluate the effects of (-)-stepholidine (SPD) on the firing activity of ventral tegmental area (VTA) dopamine (DA) neurons. SPD reversed the DA agonist apomorphine (Apo)-induced inhibition of VTA DA cell firing rate (ED50 = 4.9, 4.5-5.3 micrograms.kg-1), and the reversal was more rapid than that of a classic DA antagonist haloperidol (Hal) (ED50 = 11.2, 9.1-13.8 micrograms.kg-1). Pretreatment with SPD or Hal 0.5 mg.kg-1 attenuated Apo-induced inhibition, and SPD rendered the VTA DA cells less sensitive to larger doses of Apo (1024-4096 micrograms.kg-1) than Hal did. Pharmacological analysis indicated that the effects of SPD were mainly mediated through D2 subtype receptors. In addition, SPD increased the firing rate of VTA DA cells, while higher doses (1.4, 0.6-3.3 mg.kg-1) of SPD dramatically inactivated 4/6 of the VTA DA cells sampled. This inhibition was considered to be due to depolarization inactivation. These results suggest that SPD is a DA receptor antagonist and can effectively block the D2 autoreceptors located in the VTA DA cells.

Animals↗

PubMed1992

Comparison of effects of tetrahydropalmatine enantiomers on firing activity of dopamine neurons in substantia nigra pars compacta.

Extracellular single unit recording techniques were used to elucidate the effects of enantiomers of tetrahydropalmatine (THP) on the firing activity of dopamine (DA) neurons in substantia nigra pars compacta (SNC). (-)-THP rapidly reversed the apomorphine (Apo)-induced inhibition of the SNC DA cell firing activity (ED50 = 0.77, 0.52-1.14, mg.kg-1), while much larger doses of (+)-THP were required to reverse the Apo-induced inhibition (ED50 = 23, 15.2-34.7, mg.kg-1) and the maximal reversal caused by (+)-THP was 79 +/- 9% of the basal firing rate. In paralyzed rats, (-)-THP (0.5-16 mg.kg-1) significantly increased the spontaneous firing rate of SNC DA neurons dose-dependently, while (+)-THP did not until the dose reached 16 mg.kg-1. Pretreatment with (-)-THP 4 mg.kg-1 attenuated Apo-induced inhibition of SNC DA cell firing rate, while (+)-THP 32 mg.kg-1 revealed a similar potency to block the Apo-induced inhibition. In addition, (+)-THP did not potentiate the effect caused by d-amphetamine (Amp) as some behavioral experiments have shown, but large dose of (+)-THP (32 mg.kg-1) blocked the Amp-induced inhibition of SNC DA cell firing activity as (-)-THP (4 mg.kg-1) did. These results suggest that the interaction between D2 receptors and THP enantiomers has stereoselectivity and that (-)-THP is a D2 antagonist while (+)-THP seems to be not.

Alkaloids↗

PubMed1992

(-)-stepholidine: a dopamine receptor antagonist shows agonistic effect on rotational behavior in 6-hydroxydopamine-lesioned rats.

(-)-Stepholidine ((-)-SPD), a well demonstrated dopamine (DA) receptor antagonist in normal rats, could markedly induce contralateral rotational behavior in 6-hydroxydopamine (6-OHDA)-lesioned rats. This peculiar behavioral action of (-)-SPD, proposed to be an agonistic action on DA receptors, was further studied in this paper. The rotational behavior challenged by (-)-SPD (4 mg.kg-1, ip) or SKF-38393 (selective D1 agonist) had a gradually progressive process with a long latent period and a plateau response after 56-67 postlesion days. On the contrary, the action of apomorphine (APO) or D2 selective agonist N-0347, had a short latent period and a plateau response after d 21 of postlesion. In the latent period of rotation, (-)-SPD (4 mg.kg-1) was primed by pretreatment of APO (0.2 mg.kg-1, ip). In the period of steady contralateral rotation, a dose-dependent action of (-)-SPD was found in a range of 0.5-8 mg.kg-1 and a linear correlation (r = 0.77, P less than 0.01) between the rotation induced by (-)-SPD (4 mg.kg-1) and by APO (0.2 mg.kg-1) was also shown. These results suggest that the agonistic effect of (-)-SPD on rotation behavior in 6-OHDA-lesioned rats resembles that of D1 agonist SKF-38393. Taken together, the dual actions of (-)-SPD, antagonistic on normosensitive DA receptors and agonistic on supersensitive DA receptors, were proposed.

Animals↗

PubMed1991

[Effects of tetrahydroprotoberberines on dopamine release and 3,4-dihydroxyphenylacetic acid level in corpus striatum measured by in vivo voltammetry].

The extracellular (DA) and 3,4-dihydroxyphenylacetic acid (DOPAC) in rat striatum were measured by in vivo voltammetry to elucidate the effects of 3 tetrahydroprotoberberines on DA neurotransmission. l-tetrahydropalmatine (l-THP, 2 mg.kg-1) or l-stepholidine (l-SPD, 0.5 mg.kg-1) iv increased the striatal DA release by 225% and 233%, respectively; and l-SPD increased the DOPAC level by 70%. Moreover, the enantiomer d-THP (2 mg.kg-1) increased the DA release by 97%, and a large dose of d-THP (20 mg.kg-1) dramatically increased the extracellular DA by 1456% while it slightly elevated the DOPAC level by 123%. These results support the previous ideas that l-SPD and l-THP can block DA receptors and d-THP can deplete neuronal DA.

3,4-Dihydroxyphenylacetic Acid↗

PubMed1988