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°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°C or less. The randomly bred control group (Random DPAT Sensitive – RDS) exhibited intermediate temperature decreases (means of 1.6–1.8°C), with some 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.

Pindolol

Ritanserin

8-OH-DPAT

Saccharin

10.1097/00041444-199623000-00002

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Citations (71)

Lack of effect on naloxone on schizophrenic symptoms

American Journal of Psychiatry (1977)

David S. Janowsky David S. Segal F E Bloom Amber Abrams Roger Guillemin

10.1176/ajp.134.8.926

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Citations (99)

Suppression of alcohol and saccharin preference in rats by a novel Ca2+ channel inhibitor, Goe 5438

Psychopharmacology (1992)

Olgierd Puciłowski Amir H. Rezvani David S. Janowsky

Saccharin

Conditioned place preference

Preference test

10.1007/bf02245174

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Citations (33)

Swim test immobility co-segregates with serotonergic but not cholinergic sensitivity in cross-breeds of Flinders Line rats

Psychiatric Genetics (1994)

David H. Overstreet David S. Janowsky Olgierd Puciłowski Amir H. Rezvani

The Flinders Sensitive Line (FSL) rat, a genetic animal model of depression, was cross-bred with its normal control, the Flinders Resistant Line (FRL) rat, in order to investigate the relationship between cholinergic sensitivity, the selected variable, and two apparent genetically correlated variables, serotonergic sensitivity and swim test immobility. Cross-breeding established F1, F2 and back-cross progeny, with at least 20 rats of each sex for each group. Cholinergic sensitivity was assessed as the hypothermic response to oxotremorine (0.2 mg/kg) in 30 day old rats. Serotonergic sensitivity was assessed as the hypothermic response to 8-OH-DPAT, a serotonin (5-HT)-1A agonist, in 35-40 day old rats. Immobility was assessed as the time spent immobile in a 5 min swim test in 60-70 day old rats. For each variable, there were highly significant group differences, with the parental FSL and FRL groups being at the extremes. The segregating populations tended to be intermediate between the parental lines and were generally significantly different from both FSL and FRL groups. However, the crosses more closely resembled the FRL parent for only the cholinergic responses, the distributions for 8-OH-DPAT and immobility suggesting predominantly additive genetics. Statistical analyses with chi square to compare response distributions and regression to quantify the association between variables in the segregating populations confirmed that cholinergic sensitivity was different from serotonergic sensitivity and immobility, which were significantly correlated with each other.(ABSTRACT TRUNCATED AT 250 WORDS)

Oxotremorine

10.1097/00041444-199422000-00007

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Citations (40)

The dexamethasone suppression test and unipolar/bipolar distinctions.

PubMed (1985)

Sid Zisook David S. Janowsky John E. Overall S. Craig Risch

In an attempt to validate several subtypes of affective disorders, 52 consecutive patients hospitalized at a clinical research center were comprehensively classified along several diagnostic and phenomenologic axes. Cortisol levels of each patient were evaluated at baseline and after the administration of 0.5 and 1.0 mg dexamethasone. None of the depressive subtypes responded significantly differently to the 1.0 mg dose. However, the bipolar subtype was associated with significantly different DST responses to the 0.5 mg dose. Patients with bipolar affective disorder, both manic and depressed, had higher postdexamethasone mean cortisol levels than all other groups. The results support the distinctiveness of the bipolar diagnosis.

Dexamethasone suppression test

Optimal distinctiveness theory

Rapid cycling

Depression

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Citations (8)