Genetic influence on saline consumption and salt hypertension as exhibited by the response of various rat strains and sub-strains.

Female rats of 2 Sprague-Dawley sub-strains and of the Wistar and Fischer 344 strains were sensitized to the hypertensogenic effect of excess salt by removal of 1 kidney and by being given 1% NaCl solution as their sole drinking fluid. One of the Sprague-Dawley sub-strains (SPD) and the Wistar (CFEP) rats developed progressive saline polydipsia of equivalent degree, blood pressure rose, and about half of the members became hypertensive during treatment. Rats of the other Sprague-Dawley strain (CFNP) also showed a progressive saline intake; but although they drank substantially less saline, the incidence of hypertension among them was increased by 50%. Animals of the Fischer 344 strain displayed neither saline polydipsia--the intake remaining relatively constant at a very low level throughout the experiment--nor hypertension. Salt hypertension appears to be affected by genetic factors in at least 2 ways, one of which regulates the quantity of salt ingested (salt appetite), while the other controls the susceptibility to salt excess or perhaps to hypertension per se. Fischer 344 rats have the ability to restrict the volume consumption of saline; their resistance to enforced high salt intake has yet to be established.     

Comparison of aldosterone binding in aortic cells from Dahl salt-susceptible and salt-resistant rats

The Dahl salt-resistant substrain of Sprague-Dawley rats represents a uniform population of animals that are resistant to salt and mineralocorticoid induced hypertension. Aldosterone binding in the aortae of these rats is contrasted to that of age- and sex-matched rats of the Dahl salt-susceptible strain in an effort to identify a mechanism for resistance to salt induced hypertension. Cultured smooth muscle cells of both substrains contain two classes of aldosterone binding sites: corticoid receptor I with high affinity and low capacity, and corticoid receptor II with low affinity and high capacity. No differences were found between the two substrains in the affinities or binding capacities of these receptors. Both groups of Sprague-Dawley rats had a significantly higher corticoid receptor I affinity than the salt resistant Fischer 344 rats, a strain with a two-fold lower affinity than salt sensitive strains. These results indicate that an intrinsic defect in mineralocorticoid binding in aortic smooth muscle cells could not account for the resistance to salt and mineralocorticoid induced hypertension seen in Sprague-Dawley rats and that the biochemical abnormality underlying salt resistance is likely to be different from that of Fischer 344 rats.     

A comparison of sister chromatid exchange frequencies in peripheral lymphocytes and bone marrow cells of Fischer 344 and Sprague-Dawley rats

We have investigated spontaneous sister chromatid exchange (SCE) frequencies in peripheral lymphocytes and bone marrow cells explanted from two strains of the laboratory rat, Fischer 344 and Sprague-Dawley. A small, but significant difference was noted for both cell types, with the Fischer 344 rat being consistently higher. Other cell parameters, such as the mitotic index and the replicative index, were similar in the two strains. SCE levels in cultured peripheral lymphocytes after intraperitoneal administration of the alkylating drug cyclophosphamide (10 mg/kg) were similar for the two strains. Fischer 344 rats are known to have approximately a 10-fold higher incidence of spontaneous leukemia than do Sprague-Dawley rats. Since SCE frequency is a sensitive measure of DNA damage, our observations suggest that high leukemia incidence in the Fischer 344 rat may be related to a higher level of spontaneous DNA damage.     

Sodium excretory response to acute salt loading and induction of adrenal-regeneration hypertension in fischer 344 rats

Previous studies have shown Fischer 344 rats to be extremely resistant, if not immune to the development of salt hypertension. This is true even under the severe experimental conditions that overcome the very low susceptability of other strains such as the Long-Evans. These studies were confirmatory and also showed that the resistance could not be attributed to the ability of Fischer 344 rats to excrete salt more effectively than hypertension-prone SPD animals. Fischer 344 rats are normally susceptible to adrenal-regeneration, and not resistant to hypertension as such. Certain attributes and characteristics of strains showing resistance to salt hypertension are compared and contrasted.     

Influence of rat strain on P-glycoprotein expression in cultured hepatocytes

The amount and activity of the multi-drug transport P-glycoprotein (Pgp) have been measured in cultured hepatocytes derived from different rat strains. A marked increase in Pgp, as revealed by Western blotting, occurred 48 h after seeding in hepatocytes from Sprague-Dawley, Wistar and Fischer 344 rats, the last showing the highest value. The addition of dexamethasone (DEX) to culture medium delayed Pgp overexpression in all the strains, proportionally to the protein amount in the absence of hormone. The R-123 functional test for Pgp showed that Fischer 344 hepatocytes had the lowest ability to extrude the fluorescent dye as compared with Sprague-Dawley or Wistar rats. These results suggest that the Fischer 344 rat is more prone than other strains to culture stressing conditions, leading to an overexpression of Pgp that is not necessarily functional.Abbreviations DEX dexamethasone - FCS fetal calf serum - HRP horseradish peroxide - Pgp P-glycoprotein     

A physico-chemical comparison of aortic receptors in rat hypertension models

Rat models of genetic hypertension include spontaneous hypertension and resistance or sensitivity to mineralocorticoid and salt induced hypertension. Previously, altered aldosterone binding to corticoid receptor I was found in aortic smooth muscle cells cultured from Fischer 344 rats which are extremely resistant to steroid and salt induced hypertension. The corticoid receptor I of Fisher 344 rats had a lower affinity than that of salt sensitive Wistar-Kyoto controls, as well as spontaneously hypertensive rats and Sprague-Dawley rats. In the present study, we have used DEAE-cellulose ion exchange chromatography to compare the structure (charge properties) and steroid specificity of vascular corticoid receptor I and II sites in these same rat hypertension models. No variations in ion exchange properties of type I and II receptors were found. Together with the lower aldosterone affinity of corticoid receptor I sites in Fischer 344 rats these data suggest an altered binding domain which is not seen as a difference in charge density of the receptor protein by ion exchange chromatography.     

The effects of estradiol on pituitary responsiveness to dopamine in vitro: a comparison of ovariectomized Fischer 344 and Holtzman rats.

The objective of this study was to determine if the effectiveness of dopamine as an inhibitor of prolactin is altered by estradiol in strains of rats which show marked differences in estrogen-induced pituitary hyperplasia. Groups of Fischer 344 and Holtzman Sprague-Dawley rats were ovariectomized and implanted with Silastic capsules of estradiol. Rats were sacrificed by rapid decapitation following a brief period of ether anesthesia at 2, 4, 6, 8 weeks (F-344) or at 2 and 8 weeks (Holtzman) of estradiol treatment. The pituitary was removed and cut into fragments which were either snap frozen for initial prolactin content measurements or incubated for 60 min in the presence or absence of dopamine (1 x 10(-6) M). Prolactin was measured in the plasma, in sonicates of the pituitary and in the incubation medium by double antibody radioimmunoassay. Pituitary weight and plasma levels of prolactin were significantly less in Holtzman rats compared to Fischer 344 females at 2 or 8 weeks of estradiol treatment but pituitary concentrations of prolactin were not different between the two strains. Pituitary fragments from Fischer 344 rats studied at 2 and 4 weeks of estradiol treatment did not respond to the removal of dopamine in vitro whereas pituitary fragments from Holtzman rats obtained at 2 weeks of estradiol treatment did release significantly more prolactin in the absence than in the presence of dopamine. Pituitary fragments taken from Fischer 344 rats at 6 and 8 weeks were responsive to dopamine whereas pituitary tissue from Holtzman rats was not responsive at 8 weeks. The data indicate that temporal differences in responsiveness to the inhibitory effects of dopamine occur in strains which are susceptible or resistant to the formation of pituitary tumors following prolonged estradiol treatment.     

Endogenous digoxin-like material in normotensive and hypertensive strains of rats

We measured the concentration of endogenous digoxin-like materials (EDLM) in the serum of spontaneously hypertensive rats (SHR) and three normotensive rat strains at four stages during growth using a sensitive RIA. In the SHR, there was a significant peak in the EDLM level between 0.057-0.087 ngE/mL at 6 to 8 weeks of age, shortly after the onset of hypertension. The EDLM concentration returned to normal levels by 20 weeks of age. Sprague-Dawley and Wistar-Kyoto rats had EDLM levels below 0.050 ngE/mL at all time points studied. In contrast, Fischer 344 rats displayed persistently elevated serum EDLM concentrations that exceeded 0.124 ngE/mL from 3 to 20 weeks of life. We conclude that (1) there are significant interstrain differences in serum EDLM levels in rats; and (2) the SHR has a unique peak in serum EDLM levels at 6 to 8 weeks of age, indicating a possible role for the substance in the inception of hypertension.     

Effect of BCNU pretreatment on diquat-induced oxidant stress and hepatotoxicity

Diquat administration produces hepatic necrosis in male Fischer-344 rats, and minimally in male Sprague-Dawley rats, with massive oxidant stress observable in both strains as evidenced by increased biliary efflux of glutathione disulfide (GSSG). Pretreatment of both strains of rats with 80 mg/kg of 1,3-bis(2-chloroethyl)-N-nitrosourea (BCNU) inhibited hepatic glutathione reductase by 75 percent and increased dramatically the biliary efflux of GSSG produced by administration of diquat. BCNU pretreatment markedly potentiated diquat hepatotoxicity in the Fischer rats and modestly in Sprague-Dawley rats. BCNU-pretreated Fischer rats did not show an enhanced depletion of nonprotein sulfhydryls in response to diquat, in spite of the dramatic potentiation of the hepatic necrosis produced, nor were protein thiols depleted. The effects of BCNU on diquat hepatotoxicity in the Fischer rat are consistent with a critical role for reactive oxygen species in the pathogenesis of the observed hepatic necrosis and for the protective role of the glutathione peroxidase/reductase system. The data suggest that shifts in thiol-disulfide equilibria are not responsible for the cell death produced by oxidant stress in vivo, but are consistent with a role for lipid peroxidation in the pathogenesis of the lesion.     

Response acquisition with delayed reinforcement in Lewis and Fischer 344 rats

Previous work has shown neurochemical and behavioral differences between Lewis rats and Fischer 344 rats. Some of this work suggests that there might be differential sensitivity to delayed reinforcement between the two strains. To further explore this possibility, Lewis (n=8) and Fischer 344 (n=8) rats were exposed to a response-acquisition task with a non-resetting 20s delay to reinforcement. A tandem fixed-ratio 1, fixed-time 20s schedule of reinforcement was programmed for one of two levers; presses on the alternate lever had no programmed consequences. A greater number of Lewis rats (5/8) acquired lever pressing compared to the Fischer 344 rats (2/8). Future work with these strains may lead to a better understanding of the genetic and/or neurochemical factors involved in temporal control of behavior.     

Estrogen-induced tumors: changes in the vasculature in two strains of rat

The influence of estrogen on the vasculature of the pars distalis has been studied in two strains of rat that differ in estrogen responsiveness. (Fischer 344 rats are highly estrogen-responsive in comparison to Sprague-Dawley rats.) Ovariectomized adults were implanted with silastic capsules containing 17 beta-estradiol benzoate. Control and experimental animals were sacrificed 10 and 20 days after implantation of the silastic capsules. Pituitary weights and plasma prolactin were elevated dramatically in estrogen-treated Fischer rats in comparison to more moderate increases in Sprague-Dawley rats. Although both strains exhibited the hypertrophy of mammotrophs expected after estrogen stimulation, the vasculature in Fischer rats were dramatically altered from normal. The pars distalis of the 20-day, estrogen-treated Fischer rats contained well-formed arteries. In addition, capillaries frequently were disrupted, contributing to the formation of hemorrhagic lakes unlined by an endothelium. Even in intact capillaries, basal laminae delimiting the pericapillary spaces often were disrupted or absent. Perivascular connective tissue cells were prominent within the perivascular spaces and often contained numerous, large lysosomal dense bodies as well as clusters of small dumbbell-shaped bodies. These granule clusters also were apparent adjacent to the perivascular space within parenchymal cells, most frequently within follicular cells. The vasculature of Sprague-Dawley rats maintained a more normal appearance after estrogen treatment, although perivascular connective tissue cells did appear activated and basal laminae delimiting the pericapillary spaces were disrupted occasionally. However, no capillaries were disrupted, nor were any hemorrhagic lakes evident, and no arteries were present.(ABSTRACT TRUNCATED AT 250 WORDS)     

A characterization of gamma-glutamyltranspeptidase in normal, perinatal, premalignant and malignant rat liver

gamma-Glutamyltranspeptidase displays the following order of activity in tissues of the Fischer 344 rat: kidney much greater than small intestine much greater than cerebral cortex = testis greater than lung much greater than liver = heart. The activity of the hepatic enzyme in rats is: 4-fold higher in females than males; 4-fold higher in male Wistar, Sprague-Dawley and Zucker rats than male Fischer 344 rats; increased 10-fold in very old vs young male Fischer 344. The hepatic enzyme displays significant species variation: the mouse and rat liver enzymes are similar and low in activity, while duck, dog, pig and beef enzymes are 7, 13, 86 and 92-fold higher, respectively, in activity than the male Fischer rat liver enzyme. A liver plasma membrane isolation procedure has been devised which selects for the sinusoidal face of the liver parenchymal cell as assessed by marker enzyme analysis: for these plasma membranes the purification of gamma-glutamyltranspeptidase is 21.5 and the recovery is 42% indicating that this is the cellular and subcellular locus of the enzyme in rat liver. The characteristics of the liver plasma membrane from female rats are: pH optimum of 8.0; classical Michaelis-Menten kinetics; Km of 1.43 mM and Vmax of 33.3 nmol X mg-1 X min-1. In Fischer 344 rats, gamma-glutamyltranspeptidase activities are elevated over adult levels in perinatal liver: in fetal liver homogenates and plasma membranes the activities are increased 179 and 109-fold, respectively. The activity peaks just after birth and declines rapidly over the first 15 postnatal days. The activity of the liver enzyme in the male Fischer 344 rat exhibits a progressive increase throughout diethylnitrosamine-induced hepatocarcinogenesis: it is increased 7.8-fold in homogenates and 5.4-fold in plasma membranes at the early premalignant stage; 74-fold in homogenates and 31-fold in plasma membranes at the later hyperplastic nodular premalignant stage; and 174-fold in homogenates and 61-fold in plasma membranes at the hepatoma stage. The gradual drop in purification during hepatocarcinogenesis is associated with the appearance of the enzyme in the blood.     

Influence of age,sex and strain on the in vitro induction of unscheduled dna synthesis in rat hepatocyte primary cultures

The activity of chemical-induced unscheduled DNA synthesis was evaluated in hepatocyte primary cultures from Fischer 344 and Sprague-Dawley rats over a period of two years. In this two-year study hepatocytes from both sexes and strains were prepared from animals 2, 8, 14, 20 and 25 months of age and UDS was measured by autoradiography following treatment with N-methyl-AP-vitro-N-nitrosoguanidine and 2-acetylaminofluorine. A dose-related positive response occurred for both compounds throughout the study in hepatocytes from male and female Fischer rats and male Sprague-Dawley rats. The magnitude of the response was greatest in hepatocytes from male Fischer rats and a markedly lower response in unscheduled DNA synthesis occurred in all cultures prepared from animals of both strains and sexes at 20 and 25 months of age. Hepatocytes from female Sprague-Dawley rats showed a low level of unscheduled DNA synthesis with N-methylN-vitro-N-nitrosoguanidine throughout the study. The most striking finding was the absence of a UDS response to 2-acetylaminofuorene by hepatocytes from Sprague-Dawley females at the 8, 14, 20 or 25 month periods. The results indicate an age-related decrease in chemical-induced unscheduled DNA synthesis activity among rats.Abbreviations 2AAF 2-acetylaminofluorine[deDMSO] - dimethylsulfoxide ³H-TdR, meth yl-3H-thymidine - MNNG N-methyl-N-vitro-N-nitrosoguanidine - UDS unscheduled DNA synthesis     

Immunocytochemical analysis of prolactin cells in the adult rat adenohypophysis: distribution and quantitation relative to sex and strain

Prolactin immunocytochemistry was conducted 1) in serial sections of whole fixed pituitaries, for cell distribution analysis; and 2) on preparations of enzymatically dispersed anterior pituitary cells maintained for 1-4 days in vitro, for quantitation of the relative population of prolactin (PRL) cells. Both types of analysis were conducted on glands from young adult rats of both sexes in Long-Evans, Sprague-Dawley, and Fischer 344 strains. Cell quantitation results were compared with serum levels, intracellular content, and in vitro release of prolactin, for individual cell preparations. The results show that both PRL cell distribution and relative population numbers are similar between sexes in all three rat strains. Average percentages ranged from 25.9% to 32.1% in all young males and diestrous females. Prolactin-positive numbers of cells correlated positively with intracellular hormone content but not with serum or medium PRL levels. The prolactin cell population was significantly larger in aged Fischer 344 males but was not correlated with intracellular PRL levels. The prolactin cell population was heterogeneous in staining intensity and distribution in both sexes of all three strains.     

Strain- and sex-dependent differences in response to a single high dose of copper in the rat

Rats of either sex of the strains +/rnu, WAG/Cpb and Fischer-344 were injected i.v. with a single dose of Cu (2.5 mg/kg body weight). Hemolysis was observed in the female +/rnu and Fischer rats. Males accumulated more Cu than females in all strains. WAG/Cpb rats had higher kidney Cu concentrations. The lower hepatic Cu concentration in female Fischer rats was not caused by an increased biliary Cu excretion but by a diminished release of Cu from the blood to the liver. In both sexes the degree of hemolysis did not correlate to the Cu concentration of the erythrocytes. It is concluded that a sex-related difference exists in the metabolism of a large dose of Cu and that the Cu-induced hemolysis in females may be related to a prolonged exposure of erythrocytes to an increased Cu concentration of the plasma.     

Vascular remodeling and ET-1 expression in rat strains with different responses to chronic hypoxia

Chronic hypoxia leads to a greater degree of pulmonary hypertension in the Wistar-Kyoto (WKY) rat than in the Fischer 344 (F-344) rat. We questioned whether this difference is associated with baseline differences in pulmonary artery anatomy, a greater degree of hypoxia-induced pulmonary vascular remodeling in the WKY rat, and/or differences in expression of endothelin (ET)-1. Male F-344 and WKY rats were maintained in normoxia or normobaric hypoxia for 21 days. Morphometry revealed that baseline pulmonary artery anatomy was similar in the two strains. However, during chronic hypoxia, the WKY rats developed a greater degree of muscularization of small pulmonary arteries. Baseline plasma and lung immunoreactive ET-1 levels were similar in the WKY and F-344 rats and increased significantly during hypoxia in the WKY rats. Northern analysis demonstrated increased lung preproET-1 mRNA during hypoxia in both strains, with a greater increase in WKY rats. Immunostaining demonstrated increased ET-1 in bronchial epithelium and peripheral pulmonary arteries during hypoxia, although to a greater degree in the WKY rats. We conclude that the WKY strain demonstrates increased susceptibility to hypoxia-induced pulmonary vascular remodeling compared with the F-344 strain and that increased lung and circulating ET-1 levels during hypoxia may partly explain this difference.     

Immunity of Fischer 344 rats to salt hypertension.

Female Fischer 344 rats sensitized to the development of salt hypertension by unilateral nephrectomy were given water, 1% NaCl solution or 5% sucrose + 1% NaCl solution to drink. Rats on saline alone drank about twice the fluid volume of those on water, whereas those on the sucrose-saline solution drank four to six times as much. No Fischer 344 rats ever developed hypertension, defined as a systolic pressure exceeding 150 mm Hg, during the six months of the study. However, the group on saline averaged slightly higher arterial pressures than those on water on 13 of the 14 occasions that blood pressure was measured, and the average pressure over the entire experimental period was also significantly increased. The rats on sucrose-saline had a group mean blood pressure which was always significantly higher than that of the group on water and usually greater also than that of the group on saline, and the average pressure over the entire experimental period was significantly augmented above that in either of the other groups. Rats on either of the saline solutions also had a slight but significant degree of heart and kidney enlargement, greatest in the sucrose-saline group, which is attributed to the higher pressures developed, even though they remained within the normotensive range.     

Cryopreservation and long-term storage of primary rat hepatocytes: Effects on substrate-specific cytochrome P450-dependent activities and unscheduled DNA synthesis

The effects of cryopreservation and long-term storage on substrate-specific cytochrome P45O-dependent activities and unscheduled DNA synthesis were studied in freshly isolated and cryopreserved hepatocytes derived from adult male Fischer 344 and Sprague-Dawley rats. Primary rat hepatocytes were isolated via an in situ collagenase perfusion technique, cryopreserved at –196°C, and thawed at 5 weeks and 104 and 156 weeks post-freezing. In Fischer 344 and Sprague-Dawley rats, cryopreserved hepatocytes were equivalent or similar to freshly isolated hepatocytes in substrate-specific activities for 7-ethoxyresorufin-0-deethylase and dimethylnitrosamine-N-demethylase and unscheduled DNA synthesis responses. No significant differences in activities toward 7-ethoxyresorufin-0-deethylase and dimethylnitrosamine-N-demethylase, the substrate-specific activities for cytochromes P4501A1 and P4501A2 and cytochrome P4502E1, respectively, were observed between freshly isolated and cryopreserved hepatocytes. Similar unscheduled DNA synthesis responses, a measure of DNA damage and repair, were observed after exposure to the genotoxic carcinogens 2-acetylaminofluorene, 7,12-dimethyEbenz[a]anthracene, and dimethylnitrosamine; although some decreases were also observed in Fischer 344 hepatocytes after 104 weeks and Sprague-Dawley hepatocytes after 156 weeks in the highest concentrations tested. These results suggest that cryopreserved hepatocytes, stored for extended periods of time in liquid nitrogen, are metabolically equivalent to freshly isolated hepatocytes in their ability to activate precarcinogens.Abbreviations 2-AAF 2-acetylaminofluorene - DDH₂O distilled deionized water - DMBA 7,12-dimethyIbenz[a]anthracene - DMN dimethylnitrosamine - DMNA dimethylnitrosamine-N-demethylase - DMSO dimethyl sulfoxide - EROD 7-ethoxyresorufin-O-deethylase - F344 Fischer 344 - FBS fetal bovine serum - %IR percentage of cells in repair - LN₂ liquid nitrogen - LSD least significant difference - CG cytoplasmic grains - NNG net nuclear grains - SD Sprague-Dawley - UDS unscheduled DNA synthesis - WE Williams' Medium E     

Genetic differences in Δ9-tetrahydrocannabinol-induced facilitation of brain stimulation reward as measured by a rate-frequency curve-shift electrical brain stimulation paradigm in three different rat strains

Lewis, Fischer 344, and Sprague-Dawley rats were implanted with electrodes in the medial forebrain bundle and trained to lever press for brain stimulation reward using a ratefrequency curve-shift electrical brain stimulation paradigm based on a series of 16 pulse frequencies ranging from 25 to 141 Hz in descending order. Once reward thresholds were stable, rats were given 1.0 mg/kg Δ⁹-tetrahydrocannabinol (Δ⁹-THC), the psychoactive constituent in marijuana and hashish, or vehicle, by intraperitoneal injection. Lewis rats showed the most pronounced Δ⁹-THC-induced enhancement of brain reward functions. Sprague-Dawley rats showed an enhancement of brain reward functions that was approximately half that seen in Lewis rats. Brain reward functions in Fischer 344 rats were unaffected by Δ⁹-THC at the dose tested. These results are consistent with previous work showing Lewis rats to be highly sensitive to the rewarding properties of a variety of drugs of abuse, including opiates, cocaine, and alcohol, while Fischer 344 rats are relatively less sensitive. They extend such previous findings to cannabinoids, and further suggest that genetic variations to other cannabinoid effects may also exist.     

Hippocampal 8-[3H]Hydroxy-2-(Di-n-Propylamino)Tetralin Binding Site Densities, Serotonin Receptor (5-HT1A) Messenger Ribonucleic Acid Abundance, and Serotonin Levels Parallel the Activity of the Hypothalamopituitary-Adrenal Axis in Rat

We have previously demonstrated that susceptibility of the Lewis rat to inflammatory disease, compared with the relatively resistant Fischer F344/N rat, is related to a hyporesponsive hypothalamopituitary-adrenal axis to inflammatory and other stress mediators. Because serotonin (5-HT) and the 5-HT1A receptor are important stimulators of this axis, we have investigated the levels of 8-[3H]-hydroxy-2,3-(di-n-propylamino)tetralin binding sites, 5-HT1A mRNA, 5-HT, and 5-hydroxyindoleacetic acid in various brain regions of Lewis, outbred Harlan Sprague Dawley, and Fischer F344/N rats. Lewis rats expressed significantly fewer hippocampal and frontal cortical 8-[3H]-hydroxy-2,3-(di-n-propylamino)tetralin binding sites and less 5-HT1A mRNA than Harlan Sprague Dawley and Fischer F344/N rats. Adrenalectomy increased the number of 8-[3H]hydroxy-2,3-(di-n-propylamino)tetralin binding sites and 5-HT1A mRNA expression in the hippocampus of all three strains. Levels of hippocampal 5-HT in Fischer F344/N rats were significantly greater than levels detected in the same regions from Lewis and Harlan Sprague Dawley rats. Hypothalamic 5-HT and 5-hydroxyindoleacetic acid levels in Harlan Sprague Dawley rats were higher than the same area from the other two strains. Adrenalectomy increased the levels of 5-hydroxyindoleacetic acid in the hypothalamus of all three strains. We conclude that hippocampal 5-HT1A receptor densities and 5-HT levels in the rat parallel the activity and responsiveness of the hypothalamopituitary-adrenal axis.