mA Shock Research Articles

Diurnal variation in passive avoidance response and serum corticosterone in rats

A possible relationship between diurnal variation in performance of step-through passive avoidance response (PAR) and that in adrenocortical response was investigated. In Wistar-Imamichi strain rats, retention latency of PAR and serum corticosterone (CORT) level immediately after retention test were measured as a function of time of day. Basal CORT level was found to be low during early phase of light period, and thereafter to elevate toward dark period (Exp. 1). Eighty animals were divided into eight groups, which consisted of a combination of two diurnal times of training/testing (light phase = 14:00 and dark phase = 2:00) and four shock intensities for training (0, 0.5, 0.75, 1.0 mA) (Exp. 2). The latency of PAR was found to be longer in the light than in the dark phase, and CORT markedly increased only in the light phase in the groups with 0.75 mA. In addition, PAR was conducted at four times of day (8:00, 14:00, 20:00, 2:00) with 0.75 mA shock (Exp. 3). It was confirmed that the diurnal variation of PAR latency was associated with that the CORT elevation, with the maximum at 14:00 and the minimum at 2:00. These results indicate that diurnal variation in performance of PAR has a close relationship with that in emotional or stress response to aversive situation.

A neurochemical and behavioral investigation of the involvement of nucleus accumbens dopamine in instrumental avoidance

Two experiments were conducted to investigate the role of nucleus accumbens dopamine in the performance of a lever press avoidance task in the rat. In this task, 0.5 mA shock was presented for 5s every 30 s, but the rat could escape shock presentation, or avoid the shock for 30 s, by pressing a lever. In the first experiment, dialysis probes were implanted into the nucleus accumbens of rats previously trained on the avoidance procedure, and also two groups of untrained rats. On the day after dialysis probe implantation, rats trained to press a lever to avoid shock ( n = 10) were exposed to a 45 min avoidance test session. Untrained rats were either exposed to periodic shock ( n = 9) or the control procedure in which lights were dimmed but no shock was presented ( n = 8). Performance of the avoidance task led to significant increases in extracellular dopamine and dopamine metabolites. There was a significant positive correlation between increases in extracellular dopamine and the number of avoidance responses emitted. In the second experiment, groups of rats were trained on the lever press avoidance procedure. After training, rats received intra-accumbens injections of the neurotoxic agent 6-hydroxydopamine or ascorbic acid vehicle. Dopamine depletion produced by 6-hydroxydopamine injection led to a substantial decrease in lever pressing to avoid or escape shock. These results indicate that dopamine in nucleus accumbens is important for operant avoidance responding, and that the involvement of accumbens dopamine in instrumental behavior is not unique to positively reinforced responses.

Extinction instead of incubation following classical aversive conditioning in dogs.

Two dogs received a single paired classical conditioning trial, with tone CS and 12 mA shock US. Both dogs then showed a conditioned blood pressure increase in response to the nonreinforced CS, which extinguished with additional nonreinforced presentations. The CR showed spontaneous recovery four days later, but reextinguished with additional nonreinforced presentations. The results were interpreted as not supporting Eysenck's theory of "incubation" following one-trial aversive conditioning.

One-trial backward excitatory fear conditioning transfers across contexts

One path to human phobia may be one-trial backward fear conditioning. Human phobias transfer readily across contexts. However, animal studies of one-trial backward fear conditioning have yet to demonstrate such transfer. The present study sought to do so. It used a lick-suppression procedure with 84 naive male albino rats. Two conditioning contexts, designated O and V, were crossed factorially with two test contexts, O and V. Within each cell of the factorial design, rats received in the conditioning context either a single 12 sec tone backward paired with a single 4 sec 1 mA shock or the same tone explicitly unpaired with shock. Fear of context and fear of tone were subsequently assessed in terms of the suppression of licking that they evoked. Test results suggested that (1) the rats discriminated between contexts O and V, and (2) despite such discrimination, one-trial backward fear conditioning transfered across the two contexts. The results enhance the plausibility of one-trial backward fear conditioning as a source of human phobia.

Spinal cord alpha-2 noradrenergic receptors mediate conditioned analgesia.

The present experiment investigated the effects of direct spinal administration of the monoaminergic receptor blockers yohimbine, phentolamine and methysergide on the expression of conditioned analgesia. Animals in the Paired group received classical conditioning trials in which one context was paired with footshock administration (1 mA shock for 15 s). Animals in the Unpaired control group were administered shock in a second, different, context. On the test day animals within each condition were administered saline (20 microliters), yohimbine (30 micrograms), phentolamine (30 micrograms), or methysergide (30 micrograms) prior to receiving a hot plate test (50 degrees C) in the context previously used to shock the Paired group. These ligands were administered into the spinal fluid through a chronic, indwelling spinal catheter. Animals in the Paired group which received saline displayed longer paw lick latencies than saline-treated animals in the Unpaired group. Yohimbine, but not phentolamine or methysergide, attenuated this conditioned analgesia. These results suggest that spinal cord noradrenergic substrates mediate conditioned analgesia, and that this mediation occurs specifically through the alpha-2 noradrenergic receptor.

Antipanic drug treatments: Failure to exhibit anxiolytic-like effects on defensive burying behavior

Although the Defensive Burying paradigm has been used as a behavioral “model” for the study of anxiety and/or antianxiety agents, the effects of chronic treatment with antidepressant agents (i.e., “antipanic” agents) have not been examined in this paradigm. The present study examined the effects of two antianxiety treatments on this behavior: 1) acute treatment (30-minute pretreatment) with the benzodiazepine anxiolytic chlordiazepoxide and 2) chronic treatment (twice daily for 7–12 weeks) with the antipanic agents imipramine (IMI), desipramine (DMI) or pargyline (PARG). Prior to testing, female Sprague-Dawley rats were placed in a 40 × 30 × 40 cm Plexiglas® chamber containing clay bedding material (5 cm deep) for 30-minute periods on each of four consecutive days. On the fifth day, a wire-wrapped prod was placed at one end of the chamber. Rats were placed in the chamber individually and a 3 mA shock was delivered upon contact with the prod. Defensive Burying behavior (i.e., the moving of bedding material toward or over the prod) was recorded for 15 minutes postshock. In a dose-dependent manner, acute treatment with chlordiazepoxide reduced the frequency of occurrence of burying behavior, increased the latency to initiation of burying, and decreased the duration of burying. In contrast, chronic treatment with IMI, DMI, or PARG failed to exhibit anxiolytic-like effects on any measure of Defensive Burying. These data suggest that the Defensive Burying paradigm may not be an “animal model” for the study of panic disorder and potential antipanic agents.

Anterior and medial thalamic lesions, discriminative avoidance learning, and cingulate cortical neuronal activity in rabbits.

Four groups of male albino rabbits were trained to perform a conditioned response (CR, stepping in an activity wheel) to an acoustic (pure tone) conditional stimulus (CS+). A 1.5-2.0 mA shock unconditional stimulus (US) delivered through the grid floor of the wheel was administered 5 s after CS+ onset, but stepping during the CS-US interval prevented the US. The rabbits were also trained to ignore a second tone (a negative conditional stimulus or CS-) of different auditory frequency than the CS+, that was presented in an irregular order on half of the conditioning trials but never followed by the US. One group had bilateral electrolytic lesions in the medial dorsal (MD) thalamic nucleus, a second group had combined bilateral lesions in the MD and the anterior thalamic nuclei, and a third group had no lesions. The fourth group was composed of rabbits with combined lesions that resulted in only partial damage in the anterior and MD nuclei. In all rabbits, multi-unit activity and field potentials were recorded from the cingulate cortical projection targets of the MD and anterior nuclei. The average rate of acquisition in rabbits with MD and partial lesions was not significantly different from that in controls, but the asymptotic performance in rabbits with lesions was significantly impaired, relative to that in controls. None of the rabbits that had the combined MD and anterior thalamic lesions reached the acquisition criterion. The average proportion of trials in which these rabbits performed avoidance responses during their final training sessions was 0.3, compared to 0.8 in controls. The unconditioned response was not significantly affected by the lesions, nor was there any indication that the lesions impaired the sensory processing of the CSs. These results and the massive training-induced neuronal discharges shown in past studies to occur in the limbic thalamic neurons indicate that these neurons are importantly involved in the circuitry that mediates discriminative avoidance conditioning in rabbits. The training-induced neuronal activity in cingulate cortex was dramatically attenuated in rabbits with lesions. Differences in the degree of this attenuation between lesion conditions and with respect to training stages were discussed in relation to a theoretical working model of limbic thalamic and cingulate cortical associative functions.

Defensive burying behavior in maudsley reactive (MR/Har) and nonreactive (MNRA/Har) rats

Based upon differences in open field and conflict behaviors, the MR/Har and MNRA/Har rat strains have been proposed as a genetically-based “animal model” for the study of emotionality and/or anxiety. The present study compared the MR/Har and MNRA/Har rat strains in the Defensive Burying paradigm. Prior to testing, female MR/Har and MNRA/Har rats were placed in a 40×30×40 cm Plexiglas ® chamber containing clay bedding material (5 cm deep) for 30 minute periods on each of four consecutive day. On the fifth day, a wire wrapped prod was placed at one end of the chamber. Rats were placed in the chamber singly and a 3 mA shock was delivered upon contact with the prod. Defensive Burying behavior (i.e., the moving of bedding material toward or over the prod) was recorded for each animal for 15 minutes postshock. There was no MR/Har versus MNRA/Har difference in the percent of animals exhibiting Defensive Burying, nor was there a MR/Har versus MNRA/Har difference in the latency to initiation or the duration of this behavior. Thus, these genetically-defined Maudsley rat strains do not appear to differ in all “animal models” for the study of anxiety or fear.

Effects of cerebral depletion of norepinephrine on conditioned avoidance responding in Sprague-Dawley and Fischer rats.

Block of conditioned avoidance responding (CAR) in the rat is a property of all antipsychotic agents. To determine whether cerebral norepinephrine (NE) is crucial for CAR, the effect of depletion of cerebral NE was examined both during acquisition and retention of a CAR task in Sprague-Dawley and Fischer 344 male rats. In examining acquisition of CAR, DSP-4 [N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine] (50 mg/kg, IP) was given to naive rats from each strain. In one control group, desmethylimipramine (DMI, 20 mg/kg, IP -30 min), which inhibits the uptake of DSP-4 and its subsequent neurotoxic effect, was given prior to DSP-4. After DSP-4, all animals were tested for acquisition of CAR in a discrete trial paradigm in striatum, and brain stem were removed for NE and dopamine assay using HPLC. In examining retention of CAR, the effect of DSP-4 on the CAR of trained rats were observed. DSP-4 produced an almost total depletion of cortical NE and about 50% reduction of NE in the brain stem in both strains and in both tests. In the first experiment, DSP-4 failed to significantly diminish CAR acquisition in either strain, although there was a trend towards a DSP-4-induced deficit. Interestingly, DSP-4 caused no decrement in CAR in trained rats of either strain, but did significantly impair further acquisition of CAR in Sprague-Dawley rats. The data demonstrate cerebral NE is not critical for retention of CAR, but suggest a possible role for NE in the acquisition of CAR.

An assessment of prolactin's value as an index of stress

On an every other day basis, chronically catheterized male rats were subjected to a 30 sec grid shock in either an ascending (0.0, 0.25, 1.0, 4.0 mA) or descending order. A third group was repeatedly subjected to 1.0 mA shock over the same time frame. In 85% of the shock trials, plasma prolactin increased from baseline levels, thus indicating that prolactin is a relatively reliable index of stress. However prolactin did not change in a step-wise fashion with stressor intensity for a significant number of rats. Data from the group given repeated exposure to the 1 mA stressor showed no evidence of habituation — a process which might have explained the findings. This study indicates that prolactin levels do not sensitively track stressor intensity for individual rats.

Aversive conditioning of homozygous and heterozygous D.I. Brattleboro rats in the light-dark box

Active and passive avoidance, and conditioned freezing acquisition and retention were studied in HODI and HEDI Brattleboro rats. All animals were from the same source and of the same age and sex. The light-dark box test was employed. 0.6 and 2.0 mA footshocks were administered for the same number (7) of daily trials. Extinction time-course was followed for seven consecutive daily trials. Passive avoidance: the conditioned response was acquired and retained equally well by all Ss and for both shock intensities. Active avoidance: for 0.6 mA shocks HODI Ss acquired and retained the response significantly better than HEDI Ss; for 2.0 mA shocks the response was acquired equally by both groups of Ss, and retained significantly better by HODI Ss. Freezing: in general, HODI Ss exhibited less freezing then HEDI Ss. The diverse conditioned behavior of HODI and HEDI Ss in this paradigm, which allows the contemporaneous investigation of several aversive response, does not support the hypothesis that vasopressin deficiency impairs learning and memory in the rat.

Specific anti-aggressive effects of fluprazine hydrochloride

Two experiments were performed with adult male rats of the Long-Evans strain to determine the specificity of fluprazine hydrochloride in decreasing offensive attack. Both 4 and 8 mg/kg doses (IP) significantly reduced offense by resident males selected for high or medium levels of aggression when tested with intruders 30 min postinjection. No reliable differences in other social or nonsocial behaviors were observed. Drug treatment resulted in an overall reduction in offensive behavior of more than 70% in both groups. Actual biting and wounding of intruders by treated subjects was decreased by as much as 98%. A second experiment assessed the drug's influence on defense in the "shock-elicited aggression" paradigm. While duration of boxing to multiple intermittent shocks was significantly suppressed by drug administration (4 and 8 mg/kg), the same doses had no effect on postshock duration of boxing, or sonic and ultrasonic vocalizations following several high intensity (1.5 mA) shocks. These findings are consistent with other research on this and related phenylpiperazine compounds, indicating that its action is specific in reducing offense with minimal influence on social or defensive behavior.

Effects of Intermittent Electrical Shock on Responses Related to Milk Ejection

Electrical shock is perceived to be a problem on many dairy farms. Thirteen cows were subjected to intermittent electrical shock (5s on, 25s off) at a.m. and p.m. milkings for 7 days. Seven cows were subjected to 3.6mA shocks starting with preparation (1min udder wash and dry) and six cows to 6.0mA. One additional cow initially in the 6.0mA group had to be removed from the study because of severe behavioral responses to shock. Compared to 5-day preshock and postshock periods, milk yield, milking time, and Wisconsin Mastitis Test scores were not affected by shock. Maximum rate of milk flow increased slightly. The number of behavioral events such as lifting legs during milking increased with a greater increase in the 6.0mA group. Heart rate was elevated (+3 beats/min) only in response to shock during preparation (initial shock). For selected days, time to peak oxytocin response was delayed in the 3.6mA group, and peak prolactin and area under prolactin response curves increased similarly for both groups during shock. There were significant a.m.–p.m. differences in milk yield, milking time, maximum rate of milk flow, heart rate, and responses of oxytocin and prolactin.We think that milk yield can be maintained, at least in the short term, in cows subjected to electrical shock due to power-line problems if dairy producers take exceptional care to accommodate behavioral responses.

Effects of malnutrition and environment on the acquisition and extinction of avoidance behavior in rats

Twelve newborn rats were fed by mothers maintained on a protein-deficient diet (12% casein, M) during lactation, and 12 rats fed by mothers maintained on a diet containing 25% casein were used as controls (C). After weaning, all animals were fed standard lab ration. Half of each group was housed individually (MI and CI), while the other half was allowed to live in pairs (MP and CP). When adult, all animals were trained to avoid footshocks by jumping onto a platform. Training sessions consisted of 40 trials starting with a 20 sec light stimulus (CS) and followed by a 2 sec, 0.6 mA shock (US) with an average intertrial interval of 54 sec. When all animals displayed consistent avoidance behavior, the extinction phase was initiated. The procedure was the same as for the training sessions except that the shock generator was disconnected. Extinction continued until each animal showed a 50% reduction in avoidance performance. During acquisition, MI learned faster than CI and CI showed greater avoidance performance than CP, but no differences were observed between MP and CP. During extinction, group M responded more persistently than group C. The present acquisition results may explain the contradictory data reported in the literature with respect to the effects of malnutrition on avoidance performance, since environmental stimulation was shown to reduce the effects of early malnutrition. Individually housed animals showed greater avoidance performance during both phases.

A comparison of response prevention and massed-trials extinction in deconditioning avoidance

Sixty-four rats were trained to jump onto a safety ledge to avoid a.5 mA shock, to a criterion of 10 successive avoidance responses, and with a 30-sec inter-trial interval. They were then immediatley assigned (randomly) to one of four treatments during which shocks never occurred: massed-trials extinction, in which the inter-trial interval was reduced to 3 sec; response prevention one, in which the safety ledge was withdrawn; and response prevention two, in which the safety ledge was made inaccessible by a transparent slide. The fourth group served as a control for confinement in the responseprevention groups. The duration of the treatment was 9 minutes for all groups. Central to this study was that the duration of exposure to the fear conditioned stimulus (CS) was held constant across groups. Following treatment, all subjects were immediately retrained to the active avoidance criterion and then given normal avoidance extinction. Multivariate analysis showed that massed-trials extinction produced a greater attenuation of avoidance responding than did response-prevention, and that the responseprevention groups did not differ from each other. This confirmed the finding of Baum & Oler (1968) that massed-trials extinction is superior to response-prevention even when CS exposure duration was held constant. It is congruent with a modified two-process theory of avoidance extinction, in that massed-trials extinction provided more opportunity for the discriminative function of the CS to be modified.

An assessment of adjunctive behavior in a safety-signal paradigm

Three groups of rats were exposed to 0.4 mA shock presentations on a VT 30-sec schedule. Behavior was monitored during 35-sec shock-free periods inserted randomly after 15 of the 60 shocks per session. In the no-signal and random-signal control groups the behavior patterns which developed were similar to defense or fear reactions. In the safety-signal group, in which a tone signalled the 35-sec no-shock periods, a pattern of adjunctive and facultative behaviors developed including marked increases in grooming and rearing behaviors. No evidence of adjunctive drinking was found in any of the three groups.

Tolerance to the anti-avoidance properties of cholecystokinin-octapeptide

Previous investigations have suggested a neuroleptic-like action of cholecystokinin-octapeptide (CCK8) on conditioned-avoidance behavior. This study was initiated to test tolerance to this effect. Rats were trained to avoid electric shock in a shuttle box under a free-operant (Sidman) avoidance paradigm. Each shuttle response postponed a 0.2 sec, 1 mA shock for 20 sec. If the rat failed to respond, shock was delivered every 5 sec until a response occurred. After avoidance training, half of the rats received two daily injections of CCK8 (0.320 mg/kg, IP) and half received saline for 7 days. Rats were then tested on the Sidman avoidance 1 min after receiving CCK8 (0.640 mg/kg, IP) or saline. CCK8 depressed avoidance responding if rats received saline for 7 days prior to the test. Rats pretreated with CCK8 for 7 days were not significantly affected by CCK8 during the avoidance test. Thus, repeated injections of CCK8 result in tolerance to its anti-avoidance properties.

Septal lesions and active avoidance performance in rats: Effects of differential intrabox cues

In two separate experiments, male rats received septal lesions and were compared to operated controls on the acquisition of a two-way active avoidance task. In both experiments, an automated active avoidance apparatus (Lafayette Instrument Co.) was used, and the animals were tested 10 trials each day, 6 days/week. The CS was a tone, and the US was a 0.7 mA shock; the CS-US interval was 7 seconds. In Experiment 1, the rats (N=6/group) were tested under conventional conditions. The two compartments of the avoidance apparatus were identical in all respects. In Experiment 2, the rats (N=6/group) were tested in the same apparatus, but with differential intrabox cues. The inside of the left compartment was lined with black contact paper, while the inside of the right compartment was lined with white contact paper. Irrespective of the conditions, the septal rats were facilitated in the acquisition of shuttle-avoidance. In both tasks, the septal subjects required fewer trials to reach criterion, and showed better orientation in the shuttle-box compared to controls. The response latencies of the septal subjects also tended to be faster, but neither septal nor control subjects showed differential response latencies related to the direction of the shuttle response. Previous findings have shown that the addition of external cues to purported spatial tasks can reduce the behavioral effects produced by damage to the septohippocampal axis on such tasks. The present results suggest that such a cue-addition procedure does not influence the behavioral effects produced by septal lesions in shuttle-avoidance.

Inhibitory Conditioning Resulting from a Reduction in the Magnitude of Reinforcement

Five experiments, all employing conditioned suppression in rats, studied inhibitory conditioning to a stimulus signalling a reduction in shock intensity. Experimental subjects were conditioned to a tone signalling a 1·0 mA shock and to a tone-light compound signalling a 0·4 mA shock. On a summation test in which it alleviated the suppression maintained by a third stimulus also associated with the 1·0 mA shock, the light was established as a conditioned inhibitor. Retardation tests gave ambiguous results: the light was relatively slow to condition when paired, either alone or in conjunction with another stimulus, with the 0·4 mA shock, but the difference from a novel stimulus control group was not significant. Two final experiments found no evidence at all of inhibition on a summation test in which the light was presented in conjunction with a stimulus that had itself been associated with the 0·4 mA shock. The results of these experiments have implications for the question of what animals learn during the course of inhibitory conditioning.

Task-dependent ethanol effects on escape in rats bred for ethanol sensitivity

Lines of rats selectively bred for differences in degree of locomotor depression by ethanol were tested for ethanol-induced impairment of jumping to a descending platform to escape 0.3 mA shock. The MA (“most affected”) line showed greater decreases in height jumped than the LA (“least affected”) line at IP doses of 1.25, 1.75, and 2.25, but not a 00.75 g ethanol/kg. MA rats also showed greater increases in latency to first jump (at 1.75 and 2.25 g/kg) which largely accounted for the line difference in decrease in height jumped. Males showed greater impairment than females on both measures. While extending the greater ethanol sensitivity of MA than LA rats to impairment of an escape response, the results contrast with previous studies of water escape where the LA line showed greater impairment than the MA line.