Introversion and extroversion: implications for depression and suicidality.

A growing body of information suggests that core or underlying personality is a significant concomitant of depression and suicidality. Introversion (ie, low extroversion) is especially promising in its relationship to the phenomenology and outcome of depression, and may represent an underlying heritable trait of etiologic significance. Furthermore, the presence of introversion has implications for differentiating unipolar and bipolar depression. It is likely that introversion acts in concert with other core personality variables, including neuroticism and having a feeling-type personality to influence depression. Considering depression from the perspective of core personality allows for novel psychotherapeutic approaches based on targeting underlying personality variables.

Core heritable personality characteristics and relapse in alcoholics.

This article represents the proceedings of a symposium at the 2000 ISBRA Meeting in Yokohama, Japan. The chairs were David S. Janowsky and Jan Fawcett. The presentations were (1) The tridimensional personality questionnaire: Predictor of relapse in detoxified alcoholics, by Kurt Meszaros; (2) Novelty seeking predicts clinical trial attrition in alcoholics, by Jan Fawcett; (3) Personality and alcohol/substance use disorder patient relapse and attendance at self-help group meetings, by David S. Janowsky; and (4) A three-pathway psychobiological model for craving for alcohol, by Roel Verheul.

Over-representation of Myers Briggs Type Indicator introversion in social phobia patients.

The purpose of this study is to profile the personalities of patients with social phobia. Sixteen patients with social phobia were compared with a normative population of 55,971, and with 24 hospitalized Major Depressive Disorder inpatients, using the Myers Briggs Type Indicator. The Myers Briggs Type Indicator, a popular personality survey, divides individuals into eight categories: Extroverts versus Introverts, Sensors versus Intuitives, Thinkers versus Feelers, and Judgers versus Perceivers. Social phobia patients were significantly more often Introverts (93.7%) than were subjects in the normative population (46.2%). In addition, using continuous scores, the social phobia patients scored as significantly more introverted than did the patients with Major Depressive Disorder, who also scored as Introverted. Introversion is a major component of social phobia, and this observation may have both etiological and therapeutic significance.

Combination pharmacotherapy: a mixture of small doses of naltrexone, fluoxetine, and a thyrotropin-releasing hormone analogue reduces alcohol intake in three strains of alcohol-preferring rats.

It is common to treat some diseases with more than one medication simultaneously. Since more than one neurotransmitter system is involved in alcohol-seeking behaviour, then a therapeutic approach that targets more than one system should be more effective in reducing alcohol intake than one addressing a single system. To test this hypothesis, we compared the efficacy of low doses of individual drugs reported to reduce voluntary alcohol drinking to the efficacy of a mixture of these agents at the same low doses in reducing alcohol intake in three strains of alcohol-preferring rats (P, HAD, and Fawn-Hooded). After establishment of a stable baseline for alcohol intake in a continuous access paradigm, each rat received separate single i.p. injections of relatively low doses of either naltrexone (2.0 mg/kg), fluoxetine (1.0 mg/kg), the thyrotropin-releasing hormone analogue TA-0910 (0.2 mg/kg), a mixture of all three drugs, or the vehicle at 09:30. Each rat received all treatments, with an inter-injection washout period of at least 3 days. Alcohol and water intakes were measured at 6 and 24 h, and food intake was measured at 24 h, after the injection. Our results show that individual drugs did not significantly affect food, water, or alcohol intake. However, the mixture significantly reduced alcohol intake in all three strains, but had no effect on food intake. Similar results were obtained when the HAD rats received an oral dose of the individual drugs or the mixture. When P rats were given an i.p. injection of the mixture for 10 consecutive days, there was a continued suppressing effect. These findings show that a combination treatment designed to target simultaneously serotonergic, dopaminergic, and opioidergic systems can reduce alcohol intake, even though the doses of the individual drugs in the mixture are relatively low and ineffective when given singly.

Underlying personality differences between alcohol/substance-use disorder patients with and without an affective disorder.

The Myers-Briggs Type Indicator (MBTI), a popular personality test, was used to profile the personalities of in-patient alcoholics/substance-use disorder patients who had, and those who did not have, a concurrent affective disorder diagnosis. The MBTI divides individuals into eight categories: Extroverts and Introverts, Sensors and Intuitives, Thinkers and Feelers, and Judgers and Perceivers. Alcohol/substance-use disorder patients with no affective disorder differed from a normative population only in being significantly more often Sensing and significantly less often Intuitive single-factor types. The Extroverted/Sensing/ Feeling/Judging four-factor type was also significantly over-represented in this group, compared to a normative population. In contrast, mood-disordered alcohol/substance-use disorder patients were significantly more often Introverted, Sensing, Feeling, and Perceiving and significantly less often Extroverted, Intuitive, Thinking, and Judging single-factor types. They were also significantly more often Introverted/Sensing/ Feeling/Perceiving and Introverted/Intuitive/Feeling/Perceiving four-factor types. 'Pure' alcohol/ substance-use disorder patients differed from alcohol/substance-use disorder patients with a mood disorder in that they were significantly more often Extroverted and Thinking and significantly less often Introverted and Feeling single-factor types; and significantly less often were an Introverted/Sensing/ Feeling/Perceiving four-factor type. The above results may have psychogenetic, diagnostic, and psychotherapeutic implications.

Personality and alcohol/substance-use disorder patient relapse and attendance at self-help group meetings.

This study evaluated the role of personality in the short-term outcome of alcohol/substance-use disorder patients. Detoxifying alcohol/substance-use disorder patients were administered the Myers-Briggs Type Indicator (MBTI), the Tridimensional Personality Questionnaire (TPQ), the Michigan Alcohol Screening Test (MAST), the CAGE Questionnaire, and the Beck Depression Inventory (BDI). These patients were subsequently evaluated over a 1-month period for relapse and attendance at self-help group meetings. High TPQ Persistence scale scores predicted abstinence. When the Thinking and Feeling groups were considered separately, and when these two groups were combined into a single group, high scores for the individual groups and the combined group (i.e. Thinking and Feeling types together) predicted abstinence. High TPQ Persistence scale scores and low Shyness with Strangers and Fear of Uncertainty subscale scores predicted attendance at self-help group meetings. High MBTI Extroversion and high MBTI Thinking scores also predicted attendance at self-help group meetings. When the Extroverted and Introverted types and the Thinking and Feeling types respectively were combined, as with abstinence, high scores predicted attendance at self-help group meetings. Age, gender, CAGE, MAST, and BDI scores did not predict outcome. The above information suggests that specific personality variables may predict abstinence and attendance at self-help group meetings in recently detoxified alcoholics, and this may have prognostic and therapeutic significance.

Association between preference for sweets and excessive alcohol intake: a review of animal and human studies.

This report reviews a series of studies demonstrating a relationship between the consumption of sweets and alcohol consumption. There is consistent evidence linking the consumption of sweets to alcohol intake in both animals and humans, and there are indications that this relationship may be at least partially genetic in nature. Alcohol-preferring rats have a tendency to consume sucrose and saccharin solutions far beyond the limits of their normal fluid intake and this has been proposed to be a model of the clinical phenomenon known as loss of control. Furthermore, rats and mice, genetically bred to prefer alcohol, tend to choose more concentrated sweet solutions, compared to animals which do not prefer alcohol. Similar tendencies to prefer ultra-sweet solutions have been noted in studies of alcoholic subjects, with most alcoholics preferring sweeter sucrose solutions than do controls. Evidence also exists that those alcoholics who prefer sweeter solutions may represent a familial form of alcoholism. Finally, consumption of sweets and/or sweet solutions may significantly suppress alcohol intake in both animals and in alcoholics. Carbohydrate structure and sweet taste may contribute to this effect through different physiological mechanisms involving serotonergic, opioid, and dopaminergic functions. The possibility that there is concordance between sweet liking and alcohol consumption and/or alcoholism has theoretical, biological, and diagnostic/practical implications.

Antidepressant effects of nicotine in an animal model of depression.

Epidemiological studies indicate a high incidence of cigarette smoking among depressed individuals. Moreover, individuals with a history of depression have a much harder time giving up smoking. It has been postulated that smoking may reflect an attempt at self-medication with nicotine by these individuals. Although some animal and human studies suggest that nicotine may act as an antidepressant, further verification of this hypothesis and involvement of nicotinic cholinergic system in depressive symptoms is required. Flinders Sensitive Line (FSL) rats have been proposed as an animal model of depression. These rats, selectively bred for their hyperresponsiveness to cholinergic stimulation, show an exaggerated immobility in the forced swim test compared to their control Flinders Resistant Line (FRL) rats. Acute or chronic (14 days) administration of nicotine (0.4 mg/kg s.c.) significantly improved the performance of the FSL but not the FRL rats in the swim test. The effects of nicotine on swim test were dissociable from its effects on locomotor activity. Moreover, the FSL rats had significantly higher [3H]cytisine binding (selective for the alpha4beta2 nicotinic receptor subtype) but not [125I]alpha-bungarotoxin binding (selective for the alpha7 subtype) in the frontal cortex, striatum, midbrain and colliculi compared to FRL rats. These data strongly implicate the involvement of central nicotinic receptors in the depressive characteristics of the FSL rats, and suggest that nicotinic agonists may have therapeutic benefits in depressive disorders.

New treatments of bipolar disorder.

This clinical trials review is derived from the presentations made at the Third International Conference on Bipolar Disorder, held June 17-19, 1999 in Pittsburgh, PA, published as abstracts in Bipolar Disorders: An International Journal of Psychiatry and Neurosciences, Edited by Jair C. Soares, and Samuel Gershon. In this review, abstracts reporting on the efficacy of "third generation" anti-epileptic agents, including topiramate, lamotrigine, diphenylhydantoin, gabapentin, and the new generation antipsychotic agent, olanzapine in treating bipolar disorders are reviewed.

Myers Briggs Type Indicator and Tridimensional Personality Questionnaire differences between bipolar patients and unipolar depressed patients.

OBJECTIVES: The current study was designed to compare personality differences between bipolar patients and unipolar depressed patients, as evaluated on the Myers Briggs Type Indicator (MBTI) and the Tridimensional Personality Questionnaire (TPQ). METHODS: A group of bipolar and a group of unipolar depressed patients filled out the MBTI, the TPQ, the Beck Depression Inventory, and the CAGE questionnaire. The two groups were compared with each other as to responses on the above surveys, and subgroups of bipolar depressed and bipolar patients with manic symptoms were also compared. RESULTS: Bipolar patients were found to be significantly more extroverted (p = 0.004) and less judging (p = 0.007) on the MBTI. They were significantly more novelty seeking (p = 0.004) and less harm avoidant (p = 0.002) on the TPQ. Of the above differences, only the TPQ harm avoidance scale appeared strongly linked to the patients' level of depression. CONCLUSION: Significant differences in personality exist between bipolar disorder and unipolar depressed patients.

Preference for higher sugar concentrations and Tridimensional Personality Questionnaire scores in alcoholic and nonalcoholic men.

Animal studies have shown a positive association between the consumption of high concentrations of sweet solutions and subsequent alcohol intake. In a previous clinical study, it was shown that a preference for a high (0.83 M) concentration of sucrose (sweet liking) is characteristic of alcoholics, compared with controls. The present study was designed to determine whether personality variables, reported to be associated with subtypes of alcoholism, differentiate sweet liking alcoholics from sweet liking controls. Fifty-two male controls and 26 alcoholic patients were tested for sweet preference and administered the Tridimensional Personality Questionnaire. Sweet liking alcoholics scored significantly higher on the Tridimensional Personality Questionnaire Novelty Seeking and Harm Avoidance scales and related subscales when compared with sweet liking controls. Further analysis showed that preferred sucrose concentration, Harm Avoidance score, and Novelty Seeking predicted alcoholic versus nonalcoholic group status at 65% sensitivity and 94% specificity, with a correct classification in 85% subjects. We hypothesize that sweet liking may identify a specific alcoholism subtype also characterized by high novelty seeking and high harm avoidance. These findings may have theoretical biological significance and practical clinical implications.

Cholinergic/serotonergic interactions in hypothermia: implications for rat models of depression.

This article reviews published reports and presents new evidence that support a number of commonalties between lines of rats selectively bred for differences in cholinergic (muscarinic) and serotonergic (5-HT1A) sensitivity. The Flinders Sensitive Line (FSL) rat, a genetic animal model of depression derived for cholinergic supersensitivity, is more sensitive to both cholinergic and serotonergic agonists, and exhibits exaggerated immobility in the forced swim test relative to the control, Flinders Resistant Line (FRL), rat. Similar exaggerated responses are seen in a line of rats recently selected for increased sensitivity to the 5-HT1A agonist, 8-OH-DPAT (High DPAT Sensitive--HDS), relative to lines selectively bred for either low (Low DPAT Sensitive--LDS) or random (Random DPAT Sensitive--RDS) sensitivity to 8-OH-DPAT. For both the FSL and HDS rats, their exaggerated immobility in the forced swim test is reduced following chronic treatment with antidepressants. The present studies examined further the interaction between cholinergic and serotonergic systems in the above lines. Supersensitive hypothermic responses to 8-OH-DPAT were observed very early (postnatal day 18) in FSL rats, suggesting that both muscarinic and serotonergic supersensitivity are inherent characteristics of these rats. Scopolamine, a muscarinic antagonist, completely blocked the hypothermic effects of the muscarinic agonist oxotremorine in FSL and FRL rats, but had no effect on the hypothermic responses to 8-OH-DPAT, suggesting an independence of muscarinic and 5-HT1A systems. On the other hand, genetic selection of genetically heterogeneous rats for differential hypothermic responses to the muscarinic agonist oxotremorine were accompanied by differential hypothermic responses to 8-OH-DPAT, suggesting an interaction between muscarinic and 5-HT1A systems. Overall, these studies argue for an inherent interaction between muscarinic and 5-HT1A systems, which probably occurs beyond the postsynaptic receptors, possibly at the level of G proteins.

Potential animal model of multiple chemical sensitivity with cholinergic supersensitivity.

Multiple Chemical Sensitivity (MCS) is a clinical phenomenon in which individuals, after acute or intermittent exposure to one or more chemicals, commonly organophosphate pesticides (OPs), become overly sensitive to a wide variety of chemically-unrelated compounds, which can include ethanol, caffeine and other psychotropic drugs. The Flinders Sensitive Line (FSL) rats were selectively bred to be more sensitive to the OP diisopropylfluorophosphate (DFP) compared to their control counterparts, the Flinders Resistant Line (FRL) rats. The present paper will summarize evidence which indicates that the FSL rats exhibit certain similarities to individuals with MCS. In addition to their greater sensitivity to DFP, the FSL rats are more sensitive to nicotine and the muscarinic agonists arecoline and oxotremorine, suggesting that the number of cholinergic receptors may be increased, a conclusion now supported by biochemical evidence. The FSL rats have also been found to exhibit enhanced responses to a variety of other drugs, including the serotonin agonists m-chlorophenylpiperazine and 8-OH-DPAT, the dopamine antagonist raclopride, the benzodiazepine diazepam, and ethanol. MCS patients report enhanced responses to many of these drugs, indicating some parallels between FSL rats and MCS patients. The FSL rats also exhibit reduced activity and appetite and increased REM sleep relative to their FRL controls. Because these behavioral features and the enhanced cholinergic responses are also observed in human depressives, the FSL rats have been proposed as a genetic animal model of depression. It has also been reported that MCS patients have a greater incidence of depression, both before and after onset of their chemical sensitivities, so cholinergic supersensitivity may be a state predisposing individuals to depressive disorders and/or MCS. Further exploration of the commonalities and differences between MCS patients, human depressives, and FSL rats will help to elucidate the mechanisms underlying MCS and could lead to diagnostic approaches and treatments beneficial to MCS patients.

Suppression of alcohol intake after administration of the Chinese herbal medicine, NPI-028, and its derivatives.

The Chinese herbal medicine, NPI-028, has been used for centuries in China to counteract alcohol intoxication. The present study used a number of different experimental conditions to determine whether NPI-028 and its derivatives might selectively influence alcohol intake in rodents that naturally exhibit high alcohol intakes. It was determined that intraperitoneal (i.p.) injections of NPI-028 (0.5, 0.75, and 1.0 g/kg) suppressed alcohol intake by up to 30% in both alcohol-preferring P and Fawn-Hooded (FH) rats during a continuous access schedule. These injections did not significantly affect food or water intakes, nor did the highest dose of NPI-028 (1 g/kg) alter blood ethanol levels after an i.p. injection of 2.5 g/kg of ethanol. In P rats, it was found that NPI-028 was orally active with the dose of 1.5 g/kg having a greater effect on ethanol intake than the 1.0 g/kg dose; once again, food and water intakes were not significantly altered. In FH rats maintained on a limited access schedule (1 hr/day), alcohol intake was completely abolished by 1.5 g/kg of NPI-028. Chronic i.p. administration of NPI-028 (0.75 g/kg) for four consecutive days in FH rats maintained on a continuous access schedule did not lead to any diminution of its alcohol-suppressant effects. Thus, NPI-028 has significant effects on alcohol intake without much effect on water and food intake, and tolerance does not readily develop to these effects. The i.p. administration of a partially purified extract (NPI-031) of NPI-028, obtained by countercurrent chromatography, also dose-dependently suppressed ethanol intake in FH rats, but the highest dose 200 mg/kg) also significantly decreased food intake. Finally, the i.p. administration of puerarin (NPI-31G), an isoflavone isolated from NPI-031 by countercurrent chromatography, significantly reduced ethanol intake in FH rats without affecting food or water intake. Therefore, NPI-028 and one of its pure components, NPI-031G, selectively reduced ethanol intake in alcohol-preferring rats.

Further selection of rat lines differing in 5-HT-1A receptor sensitivity: behavioral and functional correlates.

It was previously reported that selection for differences in the hypothermic effects to the selective 5-HT-1A agonist, 8-OH-DPAT, occurred rapidly, with very substantial differences present by the fourth generation. The present communication summarizes the findings from the next five generations of selection and from behavioral and other functional studies on these rats. The rats which were more sensitive to 8-OH-DPAT (High DPAT Sensitive-HDS) exhibited decreases in temperature of 4 degrees C or more and the distribution did not overlap with that of the rats which were less sensitive to 8-OH-DPAT (Low DPAT Sensitive-LDS) which exhibited decreases in temperature of 1.5 degrees C or less. The randomly bred control group (Random DPAT Sensitive-RDS) exhibited intermediate temperature decreases (means of 1.6-1.8 degrees C), with time overlap with the distributions of the selected groups. Pretreatment with pindolol, a 5-HT-1A antagonist, reduced the hypothermic response to 8-OH-DPAT, but pretreatment with ritanserin, a 5-HT-7 and 5-HT-2A/C antagonist, had no effect, confirming that the hypothermic response to 8-OH-DPAT is mediated predominantly by 5-HT-1A receptors. The HDS rats were less mobile in a forced swim test and drank more saccharin solution in a two-bottle choice paradigm than the LDS or RDS rats over several generations. In contrast, there were no consistent differences among the groups for open field activity or performance in an elevated plus maze. There were no differences among the groups for voluntary alcohol intake, but the HDS rats exhibited greater suppression of alcohol and saccharin intake after injection of 8-OH-DPAT (0.125 mg kg-1). The HDS rats were also found to have a higher number of 5-HT-1A binding sites in cortical regions than the LDS or RDS rats, but there were no 5-HT-1A binding site differences in the raphe nuclei. These findings clearly show that consistent behavioral differences do occur in the 8-OH-DPAT-selected lines of rats, but only for behaviors related to possible depression or reward, not anxiety. The pattern of binding results suggests that these behavioral correlates of 8-OH-DPAT selection may be related to changes in cortical 5-HT-1A receptors rather than raphe autoreceptors.

Administration of antidepressants, diazepam and psychomotor stimulants further confirms the utility of Flinders Sensitive Line rats as an animal model of depression.

Flinders Sensitive Line (FSL) rats have been proposed as an animal model of depression because they resemble depressed humans in that they have elevated REM sleep, reduced activity, and increased immobility and anhedonia after exposure to stressors. The present paper reviews experiments on the drug treatment of FSL and control Flinders Resistant Line (FRL) rats related to their utility as an animal model of depression, and presents new information. FSL rats exhibited exaggerated immobility in the forced swim test which is counteracted by the tricyclic antidepressants imipramine and desipramine and the serotonin reuptake blocker sertraline; the low immobility exhibited by the FRL rats is generally unaffected by these compounds. In contrast to these "therapeutic" effects of well recognized antidepressants, lithium and bright light treatment did not alter the exaggerated immobility of FSL rats. Novel data indicated that neither FSL nor FRL rats exhibited alterations in swim test immobility following chronic administration of the psychomotor stimulant amphetamine (2 mg/kg) and the anticholinergic scopolamine (2 mg/kg), which typically reduce immobility after acute administration. However, it was found that the calcium channel blockers verapamil (5 and 15 mg/kg) and nicardipine (10 mg/kg) did reduce the exaggerated immobility in FSL rats following chronic administration, suggesting that these compounds need to be evaluated further in humans. Previous studies have indicated no differences between FSL and FRL rats evaluated in the elevated plus maze, either at baseline or after the administration of diazepam, suggesting that the FSL rat may not differ from controls in anxiety-related behavior. Another recently published study showed that the FSL rat also did not differ from normal Sprague-Dawley rats in startle tests, indicating that the FSL rats do not exhibit behaviors shown in animal models of schizophrenia. These findings confirm the utility of FSL rats as an animal model of depression because the FSL rats do not appear to exhibit behaviors analogous to anxiety or schizophrenia and because they respond "therapeutically" to antidepressants and not psychomotor stimulants.

Suppression of ethanol intake in alcohol-preferring rats by prior voluntary saccharin consumption.

In a situation offering a free choice between 0.1% saccharin solution and tap water, Fawn Hooded (FH) rats consumed 363.0 +/- 33.5 ml/kg/day of saccharin solution. Subsequently those animals drank 3.0 +/- 0.4 g/kg of ethanol in a free choice between water and 10% ethanol solution. Control FH rats that did not have access to saccharin consumed 5.0 +/- 0.5 between groups was significant: p = 0.006). When control rats were exposed to the choice between 10% ethanol solution and 0.1% saccharin solution for 4 days they consumed 383.7 +/- 27.5 ml/kg/day of saccharin solution and their ethanol intake dropped to 1.2 +/- 0.3 g/kg/day. When these rats were returned back to alcohol/water choice and exposure to saccharin was discontinued, their alcohol intake was still reduced (3.7 +/- 0.3 g/kg/day for at least 10 consecutive days). Exposure of alcohol-experienced alcohol-preferring P rats with high (6.8 +/- 0.5 g/kg/day) and stable alcohol intake to saccharin/water choice for 4 days also resulted in a significant attenuation of their ethanol intake for at least 6 days following saccharin cessation. Thus, voluntary consumption of saccharin can suppress subsequent alcohol intake in both alcohol-naive and alcohol-experienced rats.

Saccharin-induced increase in daily fluid intake as a predictor of voluntary alcohol intake in alcohol-preferring rats.

This study examined the relationship between saccharin intake and ethanol consumption in alcohol preferring (P) rats and Fawn Hooded (FH) rats before and after exposure to forced ethanol (10%, v/v) solution. Both groups exhibited large increases (> 2X) in daily fluid intake (DFI) when saccharin (0.1%, w/v) was present and exhibited moderate levels of ethanol intake. Only the P rats significantly increased their ethanol consumption after exposure to ethanol as the sole drinking fluid. Correlational analyses revealed that the absolute intakes of saccharin and ethanol were not significantly correlated in either group, but the increase in DFI in the presence of saccharin was highly correlated with ethanol intake after forced ethanol exposure (r > +0.8; p < 0.05). Similarly, when correlations were conducted for these variables over both the P and FH groups, the correlation between increase in DFI in the presence of saccharin and alcohol intake was significantly higher than that between saccharin and alcohol intakes. Reexamination of previous data from 6 different rat strains also revealed a significant correlation between increase in DFI in the presence of saccharin and ethanol intake. These findings suggest that the dramatic increase in of DFI in the presence of saccharin may be an animal analog of the clinical phenomenon known as a loss of control.

Effects of chronic mild stress on serum complement activity, saccharin preference, and corticosterone levels in Flinders lines of rats.

Complement proteins and fragments participate in the induction and modulation of specific and nonspecific immune reactions. We have examined the effect of 4 weeks of chronic mild stress (CMS) on complement sheep red blood cell hemolytic activity measured in CH50 units in two selectively bred lines of rats, the Flinders resistant line (FRL) and the Flinders sensitive line (FSL), that differ in cholinergic sensitivity and behavioral characteristics. Additionally, CMS-induced hedonic deficit (decreased preference for 0.02% saccharin over water) and serum corticosterone levels were compared in FRL and FSL rats. CMS caused a significantly (p < 0.01) greater decline in CH50 responses in FSL (-15%) than in FRL (-7%) rats. This was accompanied by a significant (p < 0.01) suppression of saccharin preference over a 24 h period in both FRL and FSL rats. Both lines showed a similar, more than 2-fold (p < 0.01) increase in corticosterone levels following CMS. These results further confirm that CMS induces a depressive-like state in rats as well as the validity of the FSL rat as a genetic model of depression. They also indicate that the effect of stress on the immune system can be monitored by measuring the complement CH50 response.