ABSTRACT
Breeding for high and low hypothermic responses to systemic administration of a serotonin1A (5-HT1A) receptor agonist (8-hydroxy-2-(di-n-propylamino)tetralin, 8-OH-DPAT) has resulted in high DPAT-sensitive (HDS) and low DPAT-sensitive (LDS) lines of rats, respectively. These lines also differ in several behavioral measures associated with stress. In the present microdialysis study we observed that basal 5-HT concentrations in the prefrontal cortex and dorsal hippocampus did not differ significantly between HDS and LDS rats. Thus, behavioral differences between the HDS and LDS lines might not be attributed to differences in basal 5-HT release. However, both lines had lower basal levels of 5-HT release than their randomly bred control group (random DPAT-sensitive, RDS) in the prefrontal cortex (mean +/- SEM, pg/20 microl, was 3.0 +/- 0.4 for LDS, 3.8 +/- 0.3 for HDS and 6.4 +/- 0.6 for RDS; F(2,59) = 5.8, P<0.005). The administration of (+/-)-fenfluramine (10 mg/kg) induced a greater increase in hippocampal 5-HT levels in HDS rats (500%) as compared with LDS (248%) or RDS (243%) rats (P<0.0001). There were no significant differences in the prefrontal cortex among lines, with a fenfluramine-induced 5-HT increase of about 900% in the three groups. This differential response to fenfluramine may be due to functional alterations of hippocampal 5-HT reuptake sites in the HDS line.
Subject(s)
8-Hydroxy-2-(di-n-propylamino)tetralin/pharmacology , Brain/drug effects , Fenfluramine/pharmacology , Receptors, Serotonin/metabolism , Selective Serotonin Reuptake Inhibitors/pharmacology , Serotonin Receptor Agonists/pharmacology , Serotonin/metabolism , Analysis of Variance , Animals , Brain/metabolism , Breeding , Cerebral Cortex/drug effects , Cerebral Cortex/metabolism , Hippocampus/drug effects , Hippocampus/metabolism , Hypothermia/metabolism , Microdialysis , Rats , Receptors, Serotonin, 5-HT1 , Species SpecificityABSTRACT
Breeding for high and low hypothermic responses to systemic administration of a serotonin1A (5-HT1A) receptor agonist (8-hydroxy-2-(di-n-propylamino)tetralin, 8-OH-DPAT) has resulted in high DPAT-sensitive (HDS) and low DPAT-sensitive (LDS) lines of rats, respectively. These lines also differ in several behavioral measures associated with stress. In the present microdialysis study we observed that basal 5-HT concentrations in the prefrontal cortex and dorsal hippocampus did not differ significantly between HDS and LDS rats. Thus, behavioral differences between the HDS and LDS lines might not be attributed to differences in basal 5-HT release. However, both lines had lower basal levels of 5-HT release than their randomly bred control group (random DPAT-sensitive, RDS) in the prefrontal cortex (mean ± SEM, pg/20 æl, was 3.0 ± 0.4 for LDS, 3.8 ± 0.3 for HDS and 6.4 ± 0.6 for RDS; F(2,59) = 5.8, P<0.005). The administration of (±)-fenfluramine (10 mg/kg) induced a greater increase in hippocampal 5-HT levels in HDS rats (500 percent) as compared with LDS (248 percent) or RDS (243 percent) rats (P<0.0001). There were no significant differences in the prefrontal cortex among lines, with a fenfluramine-induced 5-HT increase of about 900 percent in the three groups. This differential response to fenfluramine may be due to functional alterations of hippocampal 5-HT reuptake sites in the HDS line
Subject(s)
Animals , Rats , 8-Hydroxy-2-(di-n-propylamino)tetralin , Brain , Fenfluramine , Receptors, Serotonin , Serotonin , Serotonin Receptor Agonists , Selective Serotonin Reuptake Inhibitors , Analysis of Variance , Brain , Breeding , Cerebral Cortex , Hippocampus , Hypothermia , Microdialysis , Species SpecificityABSTRACT
The Flinders sensitive (FSL) and resistant (FRL) lines of rats have been selectively bred for their differences in cholinergic sensitivity. The FSL rats display hypersensitive responses to agonists of muscarinic receptors. In addition, the FSL rats display behavioral alterations that support the notion that this strain could be useful as an animal model of depression. These abnormalities include increase in rapid eye movement sleep, decrease of saccharin consumption after stress, and reduced exploratory behavior in a novel open field. On the other hand, sexual behavior is a pleasure-seeking behavior that should be altered in a mood disorder characterized by anhedonia. In the present study, spontaneous masculine sexual behavior features were analyzed, both during 30-min tests as well as during a satiety test. Results showed that, compared to outbred Sprague-Dawley (SD) rats, both the FSL and the FRL rats displayed some behavioral impairment, like a marked decrease of the ejaculatory frequency. During the satiety tests, both the FSL and the FRL rats became exhausted sooner than their SD controls. In addition to considering the present results in terms of alterations in specific neurotransmitter systems, endogamy is proposed as a possible source of the behavioral alterations.