• The Korean Journal of Physiology and Pharmacology
• /
• v.1 no.2
• /
• pp.161-167
• /
• 1997

This study compares the subtypes of central beta adrenergic receptors (ARs) of brains of untreated rats with those of imipramine-treated rats. Beta adrenergic receptors were measured by quantitative autoradiography of the binding of $^3H$-dihydroalprenolol ($^3H$-DHA) in coronal sections of rat brain. Repeated treatment of rats with imipramine significantly reduced the binding of $^3H$-DHA to beta-1 AR in many brain areas, especially throughout the cerebral cortex, hippocampus, thalamus, and amygdala. Significant reductions of the binding of $^3H$-DHA to beta-2 AR were not found in any area of the brain. These data suggests that a selective down-regulation of beta-1 AR may be involved in the adaptive changes occurring after prolonged imipramine treatment.

• Journal of the Korean Academy of Child and Adolescent Psychiatry
• /
• v.5 no.1
• /
• pp.93-101
• /
• 1994

This study was performed to assess the amount of altered serotonergic responsivity in individuals with repeated aggressive behaviors compared with normal controls. Sixteen aggressive(delinquent criminals with repeated aggressive behaviors) and seventeen controls(medical college students) were selected and assessed their severity of aggression by several psychological instruments. The platelet $^3H$-imipramine binding sites which is known to correlate the serotonergic function of the central nervous system were measured. The results are as follows. 1) Mean scores of physical aggression in the aggressive subjects were found to be significantly higher than normal controls(p<.01). And impulsivity, hostility, psychoticism in the aggressives were found higher than controls, also. 2) In the paltelet $^3H$-imipramine binding, the aggressives had a tendency of reduced maximal binding sites(Bmax) comparing with controls(p=.0841). 3) There was no statistically significant differences between two groups in the binding coefficients(Kd) of platelet $^3H$ Imipramine binding. 4) The value of maximal binding sites(Bmax) showed significant inverse correlations with aggressive scale scores of PFAV(r=-.6311), and physical aggression scale scores of CTS(r=-.5377).

• Korean Journal of Biological Psychiatry
• /
• v.1 no.1
• /
• pp.88-97
• /
• 1994

Many evidences are compatible with the correlation between the inhibition of [$^3H$] imipramine([$^3H$]IMI) and [$^3H$]paroxetine([$^3H$]PAT) binding to the 5-hydroxytryptamine(5-HT) transporter complex and the 5-HT uptake of 5-HT neurons and platelets, and most antidepressants have been shown to inhibit the [$^3H$]IMI and [$^3H$]PAT binding and the neuronal 5-HT uptake. However, several paradoxical research findings led to doubt about the pharmacological significance of the [$^3H$]IMI and [$^3H$]PAT binding sites. This study was carried to clarify the correlation between the [$^3H$]IMI and [$^3H$]PAT binding parameters and the tissue 5-HT content or/and [$^3H$]5-HT uptake in the rabbit platelet, which contains 40 times ad much 5-HT as that of human platelet and shows the 10 fold higher $B_{max}$ of the 5-HT transporter binding to a 5-HT uptake inhibitor. The rabbits were treated for 28 days with amitriptyline(4mg/kg/day : AP), fluoxetine(0.5mg/kg/day : FO), and sertraline(0.5mg/kg/day : SA) via an Alzet osmotic pump implanted for constant infusion. The [$^3H$]IMI binding $B_{max}$ and $K_d$ of the rabbit platelets were $6.4{\pm}1.2$pmol/mg protein and $10.9{\pm}2.1$nM and those in the [$^3H$]PAT binding were $8.6{\pm}1.1$pmol/mg protein and $1.6{\pm}0.3$nM, respectively. AP slightly increased $B_{max}$ of [$^3H$]IMI binding and both [$^3H$]IMI binding and [$^3H$]PAT binding $K_d$, and i contrast, it slightly decreased $B_{max}$ of [$^3H$]PAT binding. FO Slightly increased $K_d$ of both and [$^3H$]IMI and [$^3H$]PAT binding and slightly decreased $B_{max}$ of [$^3H$]IMI and [$^3H$]PAT binding. SA produced the significant increase of [$^3H$]PAT binding $B_{max}$ and the slight increase of both [$^3H$]IMI and [$^3H$]PAT binding $K_d$ and in contrast, it slightly decreased $B_{max}$ and of [$^3H$]IMI binding. And, the $V_{max}$ and $K_m$ of platelet [$^3H$]5-HT uptake were $24.2{\pm}2.4$pmol/$10^8$ platelets/min and $3.3{\pm}0.3$nM, respectively. The $V_{max}$ was little affected by AP, FO, or SA, but the [$^3H$]5-HT uptake $K_m$ value was moderately increased by FO. However, the platelet 5-HT content was moderately decreased by all of the 5-HT uptake inhibitors used in this study. These results seem to be consistent with the allosterical and competitive interaction of 5-HT uptake inhibiting antidepressants with each other as well as 5-HT in the 5-HT transporter binding, and provide no support for the view that the potencies of 5-HT uptake inhibitors to inhibit the [$^3H$]IMI or [$^3H$]PAT binding with 5-HT transporter complex correlate with their antidepressant potencies.

• The Korean Journal of Pharmacology
• /
• v.20 no.2
• /
• pp.23-34
• /
• 1984

To investigate diurnal variations of opiate receptor binding and its modification by experimental condition or treatment of various centrally-acting drugs, the amount of maximum $^3H-morphine$ binding in rat midbrain homogenates was measured at 4 hour intervals for 24 hours. Animals were conditioned under the controlled L : D, 12 : 12 cycle or D: D, 12 : 12 cycle, for 3 weeks and treated with 0.5 ml of physiological saline or drugs for 2 weeks. A highly significant diurnal rhythm with peak at 22 hour of early dark phase with an amplitude$(0.68{\pm}0.06\;pmole/mg\;protein)$ of +51.1% and nadir $(0.33{\pm}0.03\;mole/mg\;prtein)$ at 18 hour of late light phase with an amplitude of -26.6% was found in control group. 24 tour mean of $^3H-morphine$ binding was $0.45{\pm}0.03\;pmole/mg$ protein respectively. Constant dark adaptation or treatment of reserpine, pargyline, imipramine, amphetamine and chlorpromazine modified the diurnal rhythm in the time of peak and nadir binding shape, phase, amplitude of the diurnal curve and 24 hour mean of $^3H-morphine$ binding. However, Kd values were not changed in all experimental groups : Statistical analysis at times of least and great binding indicates that the differences in $^3H-morphine$ binding were due to changes not in the affinity, but in the number of binding sites. The results are interpreted with regard to the diurnal rhythm of opiate receptor finding. The modes of action of psychoactive drugs are closely related to postulated changes of receptor sensitivity in neuropharmacological aspects.

• The Korean Journal of Pharmacology
• /
• v.20 no.2
• /
• pp.35-47
• /
• 1984

Contents of immunoreactive ${\beta}-endorphin$ and maximum of $^3H-morphine$ binding was measured in the rat midbrain homogenates from different subgroups at 24 hour interval over 24 hours. Animals were adapted to the light-dark cycle(L : D, 12: 12) or constant darkness (D : D, 12 : 12) for 3 weeks. After the adaptation, 0.5ml of physiologic saline or drug was administered twice a day for 2 weeks. A highly significant circadian rhythm with the peak$(94.8{\pm}7.7\;fmole/mg\;protein)$ at 06:00 and the nadir $(27.6{\pm}2.4\;fmole/mg\;protein)$ at 18:00 was observed in constant of group. Constant dark or treatment of reserpine, pargyline, imipramine, amphetamine and chlorpromazine modified the diurnal rhythm in the time of peak and nadir, shape, phase amplitude and 24 hour mean of ${\beta}-endorphin$ contents. Opiate receptor binding by $^3H-morphine$ also showed highly significant diurnal change in control and constant dark adapted rats. Statistical analysis by one-way analysis of variance and two-way analysis of variance indicates that the·re are highly significant differences between the diurnal change of ${\beta}-endorphin$ in control and those constant dark adapted and drug treated groups. However diurnal change of Maximum $^3H-morphine$ binding is closely related to the change of ${\beta}-endorphin$ contents. The results are interpreted with regard to the circadian rhythm of beta-endorphin contents, its modification by psychoactive drugs and possible mechanism of diurnal change of opiate receptor in brain.

• The Korean Journal of Pharmacology
• /
• v.24 no.2
• /
• pp.165-178
• /
• 1988

In this study, the effect of single or repeated (daily for 7 or 14 days) electroconvulsive shock (ECS) on central and peripheral opiate system and modification of the actions of ECS by several psychoactive drugs were investigated in the rat. Repeated ECS caused increase of Met-enkephalin content and decrease of Bmax of specific $[^3H]$imorphine binding in the rat brain. These effects were persisted more than 7 days after the last ECS, but single ECS failed to show these effects. However, ${\beta}-endorphin$ content was decreased in midbrain preparation and increased in plasma by repeated or single ECS. These phenomenon was seen shortly after the last ECS. After ECS-induced seizure was prevented by phenobarbital, ECS-induced increase in Met-enkephalin content was significantly attenuated. Imipramine or pargyline did not affect the action of repeated ECS. On the other hand, reserpine, chlorpromazine or haloperidol which were classified as neuroleptic antipsychotics, augmented the ECS-induced changes of central and peripheral opiate parameters. Furthermore, in groups received repeated ECS, changes of Bmax of specific $[^3H]-morphine binding$ binding was inversely correlated with changes of Met-enkephalin contents, but not with changes of ${\beta}-endorphin$ contents. From these results, it is inferred that the central or peripheral opioidergic system may be involved in the therapeutic and/or adverse effects of ECS which also can be influenced by some psychoactive drugs.