Escape Responding Research Articles

Goldblatt hypertension and operant thermoregulation in shaved, sialoadenectomized rats

The thermobehavioral consequences of angiotensinogenic two-kidney (2K) and sodium-volume dependent one-kidney (1K) forms of Goldblatt (one-clip) renovascular hypertension were assessed in shaved, sialoadenectomized rats. The 2K group (n=8) underwent unilateral renal artery stenosis with the contralateral kidney left intact; whereas the Sham-Operation (Sham-Op) Control group (n=7) received only a laparotomy. The 1K group (n=8) underwent unilateral renal artery stenosis with contralateral nephrectomy, and the Uninephrectomy Control group (n=6) was only unilaterally nephrectomized. Shaping and testing was conducted in a convective thermal controller that permitted the experimenters to control, through continuously reinforced bar-pressing, the ambient temperature during exposure to warm (37°C) or cold (17°C) temperatures. Testing at each temperature occurred over two 6-hr sessions with an interpolated 48-hr rest period. Both 2K and 1K hypertensive rats exhibited longer durations of heat escape than their appropriate normotensive controls across both testing sessions. No differences were detected in response frequency, duration of cold escape responding, or body temperature. The results suggest that either the increased vascular resistance or the neuroendocrine-sympathetic disorder linked to the pathogenesis of Goldblatt renovascular hypertension may promote heat retention or lower heat tolerance.

Block of conditioned avoidance responding in the rat by substituted phenylpiperazines

Ortho-nethoxyphenylpiperazine (OMPP) and meta-substituted chlorophenylpiperazine (MCPP) blocked conditioned avoidance responding (CAR) in the rat ((ED 50values = 5.6 (4.6, 7.3) and 2.4 (1.9, 2.9) mg/kg i.p. (95% confidence limits), respectively) without markedly altering escape responding. Since this test predicts antipsychotic efficacy, the piperazines were examined in radioligand binding assays and found to have no affinity for dopamine (DA) binding sites, but were active at serotonin binding sites. OMPP displaced ligands for the 5-HT 1A binding site with high affinity (K i = 9.5 (5.4, 17.9) nM) but was inactive at 5-HT 2 sites (K i > 1000 nM). MCPP, on the other hand , displaced ligands for 5-HT 1, 5-HT 1A and 5-HT 2 binding sites with similar potencies (K i values = 25 (3, 67), 23 (14, 40) and 40 (33, 48) nM, respectively). Pretreatment with metergoline (1.0 mg/kg i.p. −30 min) reduced MCPP- but not OMPP-induced block of CAR. OMPP, on the other hand, acted as a DA receptor antagonist in vivo blocking amphetamine-induced stereotyped behavior, whereas MCPP did not. Neither produced catalepsy even given in doses 8–10 times those required to block CAR. Insofar as these compounds lack antidopaminergic activity in vivo, yet are active in a test (CAR) predictive of antipsychotic activity in which DA receptor antagonists are active, they may be novel antipsychotic agents, or, perhaps, false positives in the CAR paradigm.

Brain stimulation of the ventral tegmental area attenuates footshock escape: an in vivo autoradiographic analysis of opiate receptors

An in vivo autoradiographic technique was employed to visualize discrete neuroanatomical changes in opiate receptor binding as a result of aversive footshock (FS) and rewarding electrical brain stimulation (ICS). Footshock-induced escape responding was shown to be attenuated by the simultaneous presentation of non-contingent ICS. Rats were divided into 4 groups ( n = 6) receiving ICS, FS, ICS + FS or neither stimulus in an escape paradigm. During the final behavioral test session, rats were injected with 0.002 mg/kg [ 3H]diprenorphine ([ 3H]Dpr) and subsequently prepared for autoradiography. Results indicated two groups of brain areas distinguishable by their treatment-induced changes in [ 3H]Dpr binding. One group of areas included the nucleus accumbens, claustrum, claustrocortex, perirhinal cortex and ventral tegmental area. These structures showed increased binding due to both FS and ICS. The other group consisted of the diagonal band of Broca, bed nucleus of the stria terminalis, lateral hypothalamus-medial forebrain bundle and amygdala. In these regions, an increase in binding ipsilateral to the electrode was observed in animals receiving ICS with no apparent effect of FS. These results demonstrate that non-contingent ICS may not be strictly aversive and suggest an anatomic, opioid-sensitive basis for both a rewarding and aversive component of this stimulus. It appears, further, that ICS can inhibit the release of endogenous opioid peptides in areas along the mesotelencephalic dopamine pathways, possibly to regulate the activity of neurons conveying reward information. Finally, the observed changes in opiate receptor binding may indicate a mechanism for ICS to produce both drive and reward.

Drugs, environmental events and human aggressive and escape responding

Drugs, environmental events and human aggressive and escape responding

Dorso-ventral variation in the attenuating effect of lateral hypothalamic stimulation on the switch-off response elicited from the mesencephalic central gray area

Previous experiments have shown that the lateral hypothalamus (LH) is a heterogeneous structure with respect to self-stimulation and aversion. Specifically it has been reported that stimulation of the dorsal LH region entails consequences which are both more rewarding and more aversive than those due to ventral LH stimulation [5, 7, 8, 16, 18]. The aim of the present study was to compare the effects of electrical stimulation applied to either the dorsal or the ventral regions of the LH on the switch-off response elicited by activation of the dorsal part of the mesencephalic central gray area (CG). This experiment was performed using BALB/c mice. The results obtained show that whatever the LH site, hypothalamic stimulation reduces the aversive effects of CG stimulation; however, ventral LH activation was more effective than the dorsal one. In addition, a close relationship was observed between the tolerance in regard to LH stimulation alone, and the tolerance in regard to combined CG/LH stimulation. These data suggest that the more marked aversive consequences of dorsal LH stimulation represent a limiting factor for the attenuating effect on CG escape responding.

Ventral tegmental stimulation modulates centrally induced escape responding

Electrical stimulation of the ventromedial tegmentum (VT) exerts a dual effect on escape responding, induced by stimulating either the medial hypothalamus (MH) or the dorsal part of the central gray matter (CG), namely a suppressant effect which reduces MH or CG induced escape responses and a facilitating one which increases these same responses. The relative magnitude of these effects appears to depend on both the location of the VT stimulation site and the stimulation intensity applied. Furthermore, VT stimulation is often more effective in suppressing escape responding induced by MH as opposed to CG stimulation. VT stimulation has clear rewarding effects but seems to have also aversive effects. The VT sites whose stimulation induces escape suppression seem to yield less marked aversive effects than those sites whose stimulation induces escape facilitation. Furthermore, a negative correlation was found to exist between the escape rate induced by a combined CG/VT or MH/VT stimulation and the self-stimulation rate yielded by these VT sites. These results suggest that the effects of a VT stimulation on escape responding induced by electrical brain stimulation are somehow related to the rewarding and/or aversive effects of this same VT stimulation.

Effects of single and repeated daily injections of morphine, clonidine, and l-nantradol on avoidance responding of rats.

Interruption of a photobeam by rats was maintained under a continuous shock avoidance schedule, and moderate response rates were maintained at low shock frequencies. Responding decreased, and shock frequency increased, in a dose-dependent manner after acute injections of the narcotic morphine, the antihypertensive l-nantradol clonidine, and the cannabinoid l-nantradol. Clonidine and l-nantradol were about 100 times more potent than morphine for decreasing overall responding, and l-nantradol was about 3 times more potent than clonidine for decreasing escape responding. When drugs were given repeatedly prior to daily experimental sessions, tolerance developed to response rate decreases of morphine and l-nantradol within seven to ten sessions, but tolerance did not develop to rate decreases of clonidine for up to 30 sessions. Continued decreased responding by clonidine was antagonized by yohimbine, but not by prazosin or naltrexone. These results extend observations for the acute effects of l-nantradol and clonidine to operant responding under a schedule of continuous shock avoidance. Different potencies for drugs in the present and previous experiments suggest important effects of response topography on dose effects.

Morphine applied to the ventral tegmentum differentially affects centrally and peripherally induced aversive effects

In the rat, a microinjection of 15 nmoles of morphine into the ventral tegmentum (VT) was found to suppress escape responding induced by electrical stimulation applied to the dorsal part of the mesencephalic central gray. This suppressant effect (1) could be reversed by a systemic injection of naloxone and (2) was unlikely to be due to gross motor impairment since morphine injected into the VT provoked a behavioral activation. A similar microinjection of morphine into the VT did not induce analgesic effects since it did not affect the reaction thresholds to a nociceptive stimulus. The mechanisms underlying these differential effects of morphine applied to the VT are discussed.

Escape responding in a shuttlebox

Measures of response latency are a primary tool for those who investigate escape responding in rats. Unfortunately, the single term “latency to escape” has been applied to several different measures of latency. The present study was designed to demonstrate that two different measures of the “latency to escape” tap different aspects of escape responding. To that end, rats were given escape training using a Sidman Avoidance Schedule with brief inescapable electric shock as the aversive stimulus. The latency to escape the shock-shock interval, as measured from the onset of the last shock in a shock period, did not change across trials. However, the latency to escape the shock period, as measured from the onset of the first shock in a shock period, decreased across trials. In addition, the presentation of a feedback stimulus contingent upon escape responding did not affect the latency to escape either the shock period or a shock-shock interval. The results show that these two latency measures, typically not recognized as unique, measure different characteristics of the strength of escape responding in a shuttlebox. Alternative accounts of this pattern of data were considered.

Interactions between aversive and rewarding effects of hypothalamic stimulations

Interactions between aversive and rewarding effects of brain stimulations were studied by assessing the variation of both escape and approach responses induced in a shuttle box by applying electrical stimulations of various intensities simultaneously to a medial hypothalamic (MH) site and to a lateral hypothalamic (LH) site. The results obtained show that: (1) LH stimulation produces two effects whose relative strengths appear to depend on both the location of the stimulation site and the intensity applied: (a) a suppressant effect correlated with the rewarding effect, which reduces MH escape responding; and (b) an enhancing effect correlated with the aversive effect, which increases MH escape responding. (2) MH stimulation similarly produces two effects whose relative strengths vary with both the location of the stimulation site and the intensity applied: (a) an enhancing effect which increases LH approach responding and (b) a suppressant effect which decreases LH approach responding. (3) The above-mentioned effects occur irrespective of whether the two stimulation sites (MH and LH) are ipsi- or contralateral to each other. These results suggest that the effects of LH stimulation on MH induced escape as well as those of MH stimulation on LH induced approach are related to the affective (aversive, rewarding) properties of the stimulation.

Effects of dorsal raphe stimulation on escape induced by medial hypothalamic or central gray stimulation

Electrical stimulation of the ventral part of the mesencephalic central gray affects escape responding induced by stimulation of either the medial hypothalamus (MH) or dorsal central gray (CG) in the rat. The sign and magnitude of the effect appeared to depend on the following factors: (1) The location of the site stimulated in the ventral central gray and the intensity of the stimulation. A stimulation of the dorsal raphe nucleus (DR) which induced a marked rewarding and a low aversive effect reliably suppressed MH or CG induced escape. Stimulation of sites located at the boundary between DR and central gray enhanced escape at low intensities and suppressed it at higher intensities. When located more laterally in the ventral central gray, the stimulation induced less rewarding and more marked aversive effects and it reliably enhanced MH or CG induced escape. (2) The kind of stimulation applied (monopolar or bipolar). (3) The location of the site (MH or CG) from which the stimulation-induced escape responses were obtained. Furthermore, the magnitude of the suppression of escape responding thus induced was found to be positively correlated with the strength of the rewarding effect induced at the DR stimulation site. These results suggest that DR stimulation decreases the aversive effect induced by brain stimulation and that this decrease can be related to the rewarding effect of DR stimulation.

Effects of morphine on fixed interval-induced escape from food reinforcement

Pigeons were trained to respond on a fixed-interval 3-min (FI 3 min) schedule of food reinforcement. During each 1-hr session responses on a second response key produce a timeout from the FI schedule. mThe food reinforcement schedule maintained characteristic FI responding. The escape-timeout responses occurred during the period of low response rates following reinforcement. Morphine (0.25, 0.5, 1.0 mg/kg) produced dose-related rate-dependent decreases in mean fixed-interval response rates. As morphine dose increased, there was an increased tendency for the rates within the interval to converge from a variety of predrug rates to a common, low rate of responding. The effect of morphine on the schedule-induced escape responses was to increase the mean number of escapes at doses of 0.25–0.5 mg/kg and to decrease the escapes at the highest dose of 1.0 mg/kg. The mean duration of the escape-timeouts was increased by the 3 doses of the drug, with the longest durations occurring at the 0.5 mg/kg dose. There was a great deal of variability between subjects on these measures and the dose effects did not reach statistical significance. The present study extends the analysis of drug effects on schedule-induced escape to fixed-interval-induced escape responding and includes the drug morphine.

The effects of neuropeptides on discrete-trial conditioned avoidance responding

The effects of intracerebroventricular administration of several peptides on discrete-trial, conditioned avoidance responding were assessed in the rat. Three peptides (neurotensin, bombesin and beta-endorphin) produced a neuroleptic-like effect (i.e. a decrease in avoidance responding with no effect on escape responding). A low dose (0.6 nmol) of each peptide elicited a significant effect. Neurotensin and bombesin produced a significant but partial decrease in avoidance responding; larger doses of these peptides did not produce a greater effect. beta-Endorphin elicited dose-related decrements in avoidance responding. In addition, the effect of neurotensin, but not bombesin or beta-endorphin, was antagonized by simultaneous administration of an equimolar dose of thyrotropin-releasing hormone. Hence, the 3 peptides do not appear to produce decreases in avoidance responding by the same mechanism. Thyrotropin-releasing hormone, luteinizing hormone-releasing hormone, bradykinin, substance P, des-Tyr1-gamma-endorphin and melanotropin inhibiting factor did not significantly affect avoidance responding. These findings, taken together with previous findings, suggest that intracerebroventricular administration of certain endogenous peptides (neurotensin, bombesin and beta-endorphin) may exert neuroleptic-like effects.

Effects of inescapable shock on low-activity escape/avoidance responding in rats

Exposure to inescapable shock proactively interferes with the acquisition of shuttle or barpress escape responding. The learned inactivity hypothesis proposes that this deficit results primarily from the active nature of the test escape response. In support of this position, it has been demonstrated that inescapable shock not only fails to interfere with but also actually facilitates the acquisition of a low-activity escape/avoidance response. However, in this demonstration, it is unclear whether the response was emitted by the animal or elicited by the test procedure employed. The present experiment examined the effects of inescapable shock on the acquisition of a low-activity response in a context that precluded the possibility of recording elicited responses as escape/avoidance responses. We found no evidence of facilitated acquisition of the low-activity response as a result of inescapable shock. This finding, in conjunction with others, questions the data base for the learned inactivity hypothesis.

Morphine effects on escape in the rhesus monkey

The effects of 0.5, 1.0 and 2.0 mg/kg of morphine were determined in three rhesus monkeys engaged in escaping noxious electrical cutaneous shock. Morphine reduced escape responding in two subjects and increased responding in one.Analysis of these data by signal detection theory (SDT) revealed that d' was increased in two subjects and reduced in one.It was concluded that: (1) morphine has effects on behavior which vary qualitatively between subjects and are similar to those of diazepam, and (2) that SDT may be of limited value for assessing narcotic analgesia because of its inability to discriminate between narcotic and antianxiety drugs.

The effect of psychoactive drugs on operant behavior induced by microwave radiation

A total of five male CF1 mice was trained to escape from or to avoid 2.45‐GHz CW microwave radiation by emitting an operant response. The response consisted of an animal's interruption of a light beam passing through a conditioning chamber. If an animal responded while microwaves were on, radiation was terminated and remained off for 12 seconds (an escape response). If an animal responded during the off period, each response (constituting avoidance) would reset a timer that delayed the onset of microwaves for another 12 seconds. All responses involved discriminated cueing by a 2900‐Hz sonic stimulus that was paired with microwave irradiation. Averaged dose rates were approximately 45 mW g−1, but the duration of irradiation varied with the subjects' escape‐avoidance behavior. When stable baselines of responding were established, each subject was tested following administration of each of three psychoactive compounds at varying dosages: chlordiazepoxide, d‐amphetamine, and chlorpromazine. Chlordiazepoxide resulted in a decreased percentage of avoidance responding coupled with an increased percentage of escape responding. A substantial increase in the animals' cumulative exposure to microwaves was also noted when they were dosed with this drug. The data based on administration of chlorpromazine and of d‐amphetamine were highly variable both within and among subjects.

Learned helplessness and response difficulty

To determine the effects of preshock ( PS) and sex on subsequent escape learning, 32 male and 32 female rats, approximately 90- 110 days old were tested on barpress escape responding. The rats were randomly assigned to an inescapable PS treatment or the no- shock control treatment ( C). These groups were further randomly assigned to four groups of four according to a required frequency of the barpress escape response, FR 2, FR 3, FR 4, and FR 5. The results showed marked learning deficits in the PS groups at intermediate task- difficulty levels ( FR 3 and FR 4). Female C rats tended to have slightly lower mean escape latencies than male controls. There were no sex differences among the PS rats. Thus, helplessness was demonstrated at intermediate task levels ( FR 3 and FR 4), but not at extreme levels ( FR 2 and FR 5). An interesting interaction with sex was observed.

Loss and recovery of reactivity to noxious stimuli in monkeys with primary spinothalamic cordotomies, followed by secondary and tertiary lesions of other cord sectors.

Cebus albifrons monkeys were trained to escape electrical stimulation of either leg at five intensities, spanning a range from mild tingle to intense but tolerable pain, as judged by human observers who experienced the same stimuli. The average duration of stimulation received by the animals at each intensity was plotted for each leg during the period required for recovery of responsiveness to noxious electrical stimulation following ventrolateral spinal cordotomy. Recovery of escape responding was observed similarly following subsequent lesions to the spinal cord, in an attempt to define the pathways that subserve pain conduction after readjustment from cordotomies that produced substantial deficits of escape behaviour. The most enduring elevations of duration of stimulation by lesion I (left cordotomy) were produced by lesions that involved all of the ventrolateral column and most or all of one or both ventral columns. Secondary lesions of the dorsal columns, Lissauer's tract and the dorsolateral columns, in various combinations, did not produce long-term effects on escape responding. In contrast, a complete ventral hemisection produced a pronounced bilateral deficit that did not recover fully over three hundred and five post-operative days. The major conclusions are: (1) that the dorsal pathways do not play a major role in the rostral conduction of information critical for pain perception in monkeys, even though these pathways receive input from high threshold receptors; and (2) in order to produce a lasting decrease of pain sensitivity in primates by spinal surgery, the lesion must be bilateral and must involve both the ventrolateral and ventral columns.

"Learned helplessness," "learned hopefulness," and "learned obsessiveness": effects of varying contingencies on escape responding.

Two types of outcome appearing in most research on learned helplessness were studied. Subjects performing under an extinction, i.e., non-occurring, programmed outcome evidenced “learned helplessness.” Contrary to learned helplessness theory, however, most subjects given response-independent outcomes developed superstitious behavior and reported perceived control of events. Subjects in a third group whose responses were reinforced during a 50-trial “training” phase showed response “excesses” during 10 subsequent “test” trials. These results have important implications for the theory of learned helplessness and the relevance of laboratory phenomena to human behavioral disorders.

Effects of d-amphetamine on schedule-induced escape

Pigeons were trained to respond on a fixed-ratio schedule during which 90 responses produced 3 sec of grain reinforcement (FR 90). Concurrently, a separate key was available on which a response initiated a time-out from the FR schedule and turned off the discriminative stimuli associated with the FR. A second response on the same key terminated the time-out and reinstated the fixed ratio. The pigeons demonstrated a pattern of escape responding immediately following the grain reinforcement. d-Amphetamine (0.5, 1.0, 3.0 mg/kg) was administered 30 min before a probe session. During the probe sessions grain presentation was decreased to 2 sec to generate maximum escape responding. The FR response rate showed a dose related increase with doses of 0.5-1.0 mg/kg, while the same doses produced a dose related decrease in the rate of schedule-induced escape. The highest dose of 3.0 mg/kg of d-amphetamine eliminated FR and schedule-induced escape responding in all but one animal. The drug effects on a topographically similar response from the same animal during the same session suggests differential effects on schedule-controlled and schedule-induced behavior.