ABSTRACT
To date, the possible functional interaction between the dopaminergic and the somatostatinergic system during the development of the brain is unknown. This study examines whether blockage of brain dopamine receptors during fetal life might influence postnatal somatostatin (SS) receptor development. Pregnant Sprague-Dawley rats were injected intraperitoneally with either haloperidol (2.5 mg/kg/day), which blocks dopaminergic receptors, or saline. The injections were given for 16 days, commencing on the 4th or 5th day after conception (as counted from the appearance of spermatozoa in daily vaginal smear). The administration of haloperidol during gestation did not affect the levels of somatostatin-like immunoreactivity (SLI) in the two brain areas at any of the times studied. However, this treatment resulted in a decrease in the total number of receptors for 125I-Tyr11-SS in frontoparietal cortex and hippocampal plasma membranes in the 14-day-old offspring but not at 21, 35, or 60 days after birth. No significant differences in the apparent SS binding affinity values were seen after fetal exposure to haloperidol. These results suggest that the development of SS receptors in rat frontoparietal cortex and hippocampus can be transitorily delayed by fetal blockage of dopamine receptors.
Subject(s)
Brain/growth & development , Brain/metabolism , Dopamine Antagonists , Fetus/metabolism , Haloperidol/pharmacology , Receptors, Somatostatin/metabolism , Animals , Animals, Newborn , Female , Frontal Lobe/metabolism , Hippocampus/metabolism , Parietal Lobe/metabolism , Pregnancy , Rats , Rats, Sprague-Dawley , Receptors, Somatostatin/drug effects , Somatostatin/metabolismABSTRACT
The effects of withdrawal on the level and specific binding of somatostatin in the frontoparietal cortex and hippocampus of the rat after chronic haloperidol treatment were examined using 125I-Tyr11 somatostatin as tracer. One week after haloperiodol withdrawal the number of specific somatostatin receptors in both brain areas returned to control values, after having decreased as the result of chronic administration. Neither administration of haloperidol nor withdrawal of it affected the levels of somatostatin-like immunoreactivity (SLI) in the two brain areas studied. The return of the somatostatin receptor number to control values after haloperidol withdrawal may be related to the motor side-effects that are clinically observed when the haloperidol treatment is terminated.
Subject(s)
Brain/metabolism , Haloperidol/pharmacology , Somatostatin/metabolism , Substance Withdrawal Syndrome/metabolism , Animals , Binding, Competitive , Brain/drug effects , Male , Radioimmunoassay , Rats , Rats, Inbred Strains , Receptors, Neurotransmitter/drug effects , Receptors, Neurotransmitter/metabolism , Receptors, SomatostatinABSTRACT
The effects of short and long-term haloperidol treatment on somatostatin concentration and specific binding in rat cerebral cortex and hippocampus were examined using the binding ligand 125I-Tyr1-somatostatin. Haloperidol treatment did not affect the concentration of somatostatin-like immunoreactivity in the two brain areas. Nevertheless, long-term, and not short-term, haloperidol treatment decreased the number of somatostatin receptors in the cerebral cortex and hippocampus. No significant differences in the apparent binding affinity values were seen after haloperidol treatment. When added at the time of the binding assay haloperidol 34.2 microM produced a 42% and 27% decrease in cerebrocortical and hippocampal membrane somatostatin receptors respectively.
Subject(s)
Haloperidol/administration & dosage , Receptors, Neurotransmitter/drug effects , Somatostatin/metabolism , Animals , Cerebral Cortex/drug effects , Cerebral Cortex/metabolism , Hippocampus/drug effects , Hippocampus/metabolism , Male , Radioimmunoassay , Rats , Rats, Inbred Strains , Receptors, Somatostatin , Time FactorsABSTRACT
Rats were kindled by intraperitoneal injection of pentylenetetrazol (PTZ) (30 mg/Kg) every 48 h. Once kindled, some of the animals received a single injection of cysteamine (200 mg/Kg). Somatostatin-like immunoreactivity (SLI) and 125 I-Tyr11-somatostatin binding were measured in the frontoparietal cortex and hippocampus of the two experimental groups and the control rats. After PTZ kindling the following was observed: 1) SLI content was increased in the two areas; 2) Somatostatin receptor affinity decreased in the frontoparietal cortex and was unaltered in the hippocampus; 3) The number of somatostatin receptors decreased in the hippocampus and was unaltered in the frontoparietal cortex. Cysteamine, an agent which depletes brain somatostatin and suppresses kindled seizures in PTZ-treated rats, reversed the altered SLI levels and binding in these rats.