Learned helplessness: effects of response requirement and interval between treatment and testing.

Three experiments investigated learned helplessness in rats manipulating response requirements, shock duration, and intervals between treatment and testing. In Experiment 1, rats previously exposed to uncontrollable or no shocks were tested under one of four different contingencies of negative reinforcement: FR 1 or FR 2 escape contingency for running, and FR1 escape contingency for jumping (differing for the maximum shock duration of 10s or 30s). The results showed that the uncontrollable shocks produced a clear operant learning deficit (learned helplessness effect) only when the animals were tested under the jumping FR 1 escape contingency with 10-s max shock duration. Experiment 2 isolated of the effects of uncontrollability from shock exposure per se and showed that the escape deficit observed using the FR 1 escape jumping response (10-s shock duration) was produced by the uncontrollability of shock. Experiment 3 showed that using the FR 1 jumping escape contingency in the test, the learned helplessness effect was observed one, 14 or 28 days after treatment. These results suggest that running may not be an appropriate test for learned helplessness, and that many diverging results found in the literature might be accounted for by the confounding effects of respondent and operant contingencies present when running is required of rats.

Behavioral effects of 5-HT receptor ligands in the aversive brain stimulation, elevated plus-maze and learned helplessness tests.

In order to illustrate the use of animal models in the study of the anxiolytic and antidepressant properties of drugs acting on 5-HT receptors, a series of experiments is described. With electrical stimulation of the midbrain central gray (CG), an aversive area of the brain, the 5-HT-1 receptor antagonist propranolol raised the aversive threshold in a dose-dependent way, following its microinjection into the CG. This antiaversive effect of propranolol, which is similar to that of benzodiazepine anxiolytics, was prevented by microinjection into the same brain site of the 5-HT-2 receptor blocker ritanserin. Ritanserin itself and the 5-HT-1A receptor ligand ipsapirone caused either little or no effect. In another animal model of anxiety, the elevated plus-maze, intra-CG propranolol also caused an anxiolytic-like effect, antagonized by ritanserin, indicating a 5-HT mediation. However, systemically injected isamoltane, a congener of propranolol, was ineffective in the elevated plus-maze, whereas ipsapirone caused an anxiolytic effect. Ritanserin was again inactive. Finally, both ipsapirone as well as another 5-HT-1A receptor ligand BAY R 1531, given IP, reversed the learning deficit resulting from exposure to uncontrollable foot-shocks, an effect characteristic of antidepressant drugs.

Opioid nature of learned helplessness and stress induced analgesia observed without re-exposure to shock.

It has been shown that uncontrollable shocks that produce learned helplessness also produce long-term opioid analgesia if th animal is re-exposed to shock immediately before the test. The present study was conducted in order to investigate if this effect can be observed 24h after the uncontrollable shock treatment without re-exposure to shock, and if it is opioid mediated. Long-term analgesia was found in the absence of re-exposure to shock, and was prevented by an i.p. injection of naloxone (10mg/kg) administered 10min before the test. The learned helplessness effect produced by the same shock treatment was prevented by the administration of 10 and 20mg/kg of naloxone 10min before the shuttlebox test, but not by a lower naloxone dose (5mg/kg). These findings suggest that the shock re-exposure requirement proposed in previous studies is not crucial in determining the long-term analgesia, and that both the long-term analgesia and the learned helplessness effect produced by this shock treatment were opioid mediated.

Effects of ipsapirone and BAY R 1531 on learned helplessness.

The effects of the 5-hydroxytryptamine-1A (5-HT1A) receptor agonists on the learned helplessness test were investigated. Rats were submitted to a single session of 60 uncontrollable shocks (10-s duration, 1.0 mA, every 60 +/- 40 s) and then treated twice daily with ip injections of either ipsapirone (13 mg/kg daily) or BAY R 1531 (0.375 mg/kg daily) for four consecutive days. On the last day, the animals were submitted to an escape test. The results showed that both drug treatments blocked the deficit in the escape learning (helplessness effect). These data suggest that drugs which stimulate 5-HT1A receptors have an antidepressant-like activity in this animal model of depression.

Behavioral variability in SHR and WKY rats as a function of rearing environment and reinforcement contingency.

The spontaneously hypertensive rat (SHR) may model aspects of human attention deficit hyperactivity disorder (ADHD). For example, just as responses by children with ADHD tend to be variable, so too SHRs often respond more variably than do Wistar-Kyoto (WKY) control rats. The present study asked whether behavioral variability in the SHR strain is influenced by rearing environment, a question related to hypotheses concerning the etiology of human ADHD. Some rats from each strain were reared in an enriched environment (housed socially), and others were reared in an impoverished environment (housed in isolation). Four groups--enriched SHR, impoverished SHR, enriched WKY, and impoverished WKY--were studied under two reinforcement contingencies, one in which reinforcement was independent of response variability and the other in which reinforcement depended upon high variability. The main finding was that rearing environment did not influence response variability (enriched and impoverished subjects responded similarly throughout). However, rearing environment affected body weight (enriched subjects weighted more than impoverished subjects) and response rate (impoverished subjects generally responded faster than enriched subjects). In addition, SHRs tended to respond variably throughout the experiment, whereas WKYs were more sensitive to the variability contingencies. Thus, behavioral variability was affected by genetic strain and by reinforcement contingency but not by the environment in which the subjects were reared.

Effects of ipsapirone and BAY R 1531 on learned helplessness

The effects of the 5-hydroxytryptamine-1A (5-HT1A) receptor agonists on the learned helplessness test were investigated. Rats were submited to a single session of 60 uncontrollable shocks (10-s duration, 1.0 mA, every 60 + or - 40 s) and then treated twice daily with ip ijections of either ipsapirone (13 mg/kg daily) or BAY R 1531 (0.375 mg/kg daily) for four consecutive days. On the last day, the animals were submitted to an escap test. The results showed that both drug treatments blocked the deficit in the escape learning (helplessness effect). These data suggest that drugs which stimulate 5-HT1A receptors have an antidepressant-like activity in this animal model of depression