- Email: [email protected]
Dopaminergic modulation of dye coupling between nucleus accumbens neurons: Evidence for D1–D2 interaction
246
recall (F[3,27]=1.54, p=O.23), while immediate recall improved (F[3,30]= 5.56, p=O.O04), specifically from day I vs. 12 (F[ 1,10]=9.09, p=O.Ol). Despite evidence of overall cognitive impairment in the schizophrenics, they were less rather than more sensitive to the DEX-effect on declarative memory than normals. Plasma cortisol decreased in both DEX-treated groups, although less in some schizophrenics. These results demonstrate 1) a selective DEX-effect on declarative memory in normals, and 2) a dissociation in schizophrenia between modest HPA insensitivity and marked cognitive insensitivity to DEX. Research should address whether the DEX-effect on memory occurs via hippocampal GC receptors, which may show reduced binding in schizophrenia.
EFFECTS OF WITHDRAWAL FROM NEUROLEPTIC TREATMENT ON DOPAMINE AND GABA RELEASE IN DORSOLATERAL STRIATUM OF THE CONSCIOUS RAT. AN IN VIVO MICRODIALYSIS STUDY W.T. O’Connor*, R. Schwartz, Pharmacology Stockholm,
S. Lillrank, K. Kramlinger,
U. Ungerstedt Dept.. Karolinsku
Institute,
Box 60-400,
S104-01
Sweden
Withdrawal from chronic treatment with conventional neuroleptics results in supersensitivity of both autoreceptors on DA terminals and postynaptic DA receptors on GABAergic medium sized spiny neurons in the DLS and may underlie the extrapyramidal side effects associated with these treatments. SCH23390 (SCH), clozapine (CLZ), haloperidol (HAL) or raclopride (RAC) were administered orally (CLZ. HAL and RAC) or by S.C. injection (SCH) for 30 days to separate groups of rats. Microdialysis probes were implanted into the DLS and 60 hrs following drug withdrawal, basal extracellular DA levels (3.63k.77 nM) were reduced in the HAL (-64%) and RAC (-48%) treated rats while basal GABA levels (17.4f2.28 nM) were increased (+54%) in the RAC treated rats. The results show a marked difference in the effect of withdrawal from the different neuroleptics on DA and GABA release and suggest that subtypes of the DA D2 receptor may differentially regulate DA and GABA release in the DLS.
DOPAMINERGIC MODULATION OF DYE COUPLING BETWEEN NUCLEUS ACCUMBENS NEURONS: EVIDENCE FOR D 1-D2 INTERACTION P. O’Donnell*, Department Pittsburgh
A.A. Grace
of Behavioral PA 15260, USA
Neuroscience.
Unil,. of Pittsburgh.
The presence of dye coupling and electrotonic coupling between neurons within the nucleus accumbens was examined using intracellular recording and staining in rat brain slices. Injection of single accumbens neurons with the dye Lucifer yellow resulted in the complete labelling of two or more cells in 24% of the cases. In the posterior part of the shell region, D, receptor stimulation increased the incidence of coupling (control: 6.3% (1116); D?: 54.5% (6/l]); p=O.O09, Fisher exact test). On the other hand, D, receptor stimulation induced a significant decrease in the incidence of dye coupling in the core region of the accumbens (control: 25.8% (g/31); D,: 0% (O/13; p=O.O4). Furthermore, events recorded in core neurons that resembled electrotonic coupling potentials were reversibly attenuated by administration of the D, agonist SKF 38393 (3 mM). Administration of apomorphine also reduced the incidence of coupling between core cells, and this effect could be blocked by perfusing the slices with either a D, or a DZ antagonist. In slices obtained from rats pretreated with reserpine and the dopamine synthesis inhibitor cx-MPT, D, agonist administration did not alter coupling between core cells. However, the efficacy of the D, agonist was restored in the dopamine-depleted slices if a Dz agonist is also administered. Therefore, although DZ receptor stimulation alone is sufficient to increase dye coupling in the posterior shell region of the accumbens, a basal level of Dz receptor stimulation must be present in the core region to enable D, agonists to decrease coupling between cells (D,: 22% (4/18); Dz: 0% (O/23); p=O.O3). These findings suggest that dopamine, in addition to its actions on the membrane of single neurons, may also influence the network properties of the accumbens by regulating the transfer of information between adjacent neurons within this brain region.
HIGH AND LOW DOSE OF CLOZAPINE COMPARED IN A DOUBLE-BLIND STUDY S.G. Potkin*,
R. Bera,
B. Gulasekaram,
Y. Jin, J. Wu,
J. Costa, B. Gerber, G. Richmond, D. Ploszaj, D. Carreon, T. Cooper, K. Sitanggan Department Medical
ofPsychiatry,
Center,
Orange,
Unil’ersity CA 92668,
of California
Inine
USA
Chronic schizophrenic patients were randomly assigned to 400 mg or 800 mg/day of clozapine in a 12-week double-blind study to assess efficacy and side effects. Patients were hospitalized at University of California Irvine Medical Center or Metropolitan State Hospital at the time of admission to the study and remained hospitalized as long as clinically necessary. All patients were titrated to 400 mg/day by the end of the third week. The 800 mg/day group was titrated to 800 mg/day during the sixth and seventh weeks and remained on 800 mg/day for the rest of the 12 weeks. Data from the first 25 patients demonstrated that both treatments are highly effective (repeated measures ANOVA F(5,115)=5.65, p
recall (F[3,27]=1.54, p=O.23), while immediate recall improved (F[3,30]= 5.56, p=O.O04), specifically from day I vs. 12 (F[ 1,10]=9.09, p=O.Ol). Despite evidence of overall cognitive impairment in the schizophrenics, they were less rather than more sensitive to the DEX-effect on declarative memory than normals. Plasma cortisol decreased in both DEX-treated groups, although less in some schizophrenics. These results demonstrate 1) a selective DEX-effect on declarative memory in normals, and 2) a dissociation in schizophrenia between modest HPA insensitivity and marked cognitive insensitivity to DEX. Research should address whether the DEX-effect on memory occurs via hippocampal GC receptors, which may show reduced binding in schizophrenia.
EFFECTS OF WITHDRAWAL FROM NEUROLEPTIC TREATMENT ON DOPAMINE AND GABA RELEASE IN DORSOLATERAL STRIATUM OF THE CONSCIOUS RAT. AN IN VIVO MICRODIALYSIS STUDY W.T. O’Connor*, R. Schwartz, Pharmacology Stockholm,
S. Lillrank, K. Kramlinger,
U. Ungerstedt Dept.. Karolinsku
Institute,
Box 60-400,
S104-01
Sweden
Withdrawal from chronic treatment with conventional neuroleptics results in supersensitivity of both autoreceptors on DA terminals and postynaptic DA receptors on GABAergic medium sized spiny neurons in the DLS and may underlie the extrapyramidal side effects associated with these treatments. SCH23390 (SCH), clozapine (CLZ), haloperidol (HAL) or raclopride (RAC) were administered orally (CLZ. HAL and RAC) or by S.C. injection (SCH) for 30 days to separate groups of rats. Microdialysis probes were implanted into the DLS and 60 hrs following drug withdrawal, basal extracellular DA levels (3.63k.77 nM) were reduced in the HAL (-64%) and RAC (-48%) treated rats while basal GABA levels (17.4f2.28 nM) were increased (+54%) in the RAC treated rats. The results show a marked difference in the effect of withdrawal from the different neuroleptics on DA and GABA release and suggest that subtypes of the DA D2 receptor may differentially regulate DA and GABA release in the DLS.
DOPAMINERGIC MODULATION OF DYE COUPLING BETWEEN NUCLEUS ACCUMBENS NEURONS: EVIDENCE FOR D 1-D2 INTERACTION P. O’Donnell*, Department Pittsburgh
A.A. Grace
of Behavioral PA 15260, USA
Neuroscience.
Unil,. of Pittsburgh.
The presence of dye coupling and electrotonic coupling between neurons within the nucleus accumbens was examined using intracellular recording and staining in rat brain slices. Injection of single accumbens neurons with the dye Lucifer yellow resulted in the complete labelling of two or more cells in 24% of the cases. In the posterior part of the shell region, D, receptor stimulation increased the incidence of coupling (control: 6.3% (1116); D?: 54.5% (6/l]); p=O.O09, Fisher exact test). On the other hand, D, receptor stimulation induced a significant decrease in the incidence of dye coupling in the core region of the accumbens (control: 25.8% (g/31); D,: 0% (O/13; p=O.O4). Furthermore, events recorded in core neurons that resembled electrotonic coupling potentials were reversibly attenuated by administration of the D, agonist SKF 38393 (3 mM). Administration of apomorphine also reduced the incidence of coupling between core cells, and this effect could be blocked by perfusing the slices with either a D, or a DZ antagonist. In slices obtained from rats pretreated with reserpine and the dopamine synthesis inhibitor cx-MPT, D, agonist administration did not alter coupling between core cells. However, the efficacy of the D, agonist was restored in the dopamine-depleted slices if a Dz agonist is also administered. Therefore, although DZ receptor stimulation alone is sufficient to increase dye coupling in the posterior shell region of the accumbens, a basal level of Dz receptor stimulation must be present in the core region to enable D, agonists to decrease coupling between cells (D,: 22% (4/18); Dz: 0% (O/23); p=O.O3). These findings suggest that dopamine, in addition to its actions on the membrane of single neurons, may also influence the network properties of the accumbens by regulating the transfer of information between adjacent neurons within this brain region.
HIGH AND LOW DOSE OF CLOZAPINE COMPARED IN A DOUBLE-BLIND STUDY S.G. Potkin*,
R. Bera,
B. Gulasekaram,
Y. Jin, J. Wu,
J. Costa, B. Gerber, G. Richmond, D. Ploszaj, D. Carreon, T. Cooper, K. Sitanggan Department Medical
ofPsychiatry,
Center,
Orange,
Unil’ersity CA 92668,
of California
Inine
USA
Chronic schizophrenic patients were randomly assigned to 400 mg or 800 mg/day of clozapine in a 12-week double-blind study to assess efficacy and side effects. Patients were hospitalized at University of California Irvine Medical Center or Metropolitan State Hospital at the time of admission to the study and remained hospitalized as long as clinically necessary. All patients were titrated to 400 mg/day by the end of the third week. The 800 mg/day group was titrated to 800 mg/day during the sixth and seventh weeks and remained on 800 mg/day for the rest of the 12 weeks. Data from the first 25 patients demonstrated that both treatments are highly effective (repeated measures ANOVA F(5,115)=5.65, p