Avoidance Responding In Rats Research Articles

Evaluation of the effects of α2 adrenoceptor antagonism with the D2 receptor antagonist raclopride on conditioned avoidance responding in rats

The α2 adrenoceptor antagonist idazoxan, when combined with a subeffective dose of the D2 receptor antagonist raclopride or other D2 receptor antagonists, produces inhibition of conditioned avoidance responding (CAR) in rats, an effect predictive of antipsychotic effects. In other models, this treatment combination indicates putative atypical antipsychotic effects as well, and has led to a α2/D2 receptor hypothesis for atypicality. However, this hypothesis would be better supported if other α2 adrenoceptor antagonists were investigated and the role of the alternative mechanisms, particularly 5-HT1A receptor agonism, for the behavioral effects of idazoxan were evaluated. This study sought to further test the α2/D2 receptor hypothesis by assessing the effects of α2, D2 and 5-HT1A receptor ligands on CAR in rats. Raclopride significantly reduced CAR. Administration of idazoxan or the α2 adrenoceptor antagonist yohimbine with a subeffective dose of raclopride also significantly reduced CAR. Pretreatment with the 5-HT1A receptor antagonist WAY100635 failed to significantly reverse the inhibition of CAR produced by the idazoxan and raclopride treatment combination. To the extent that 5-HT1A receptor antagonism failed to block the effects of idazoxan in combination with raclopride on CAR, α2 adrenoceptor antagonism alone appears to potentiate the putative antipsychotic effects produced through D2 receptor antagonism.

Avoidance responding following amphetamine-induced dopamine depletion.

The effect of an amphetamine-induced depletion of striatal dopamine on active and passive avoidance responding of rats was examined. Sixteen animals received two sets of 4 injections each of 15 mg/kg d-amphetamine, administered at 2 hr intervals with each set delivered one week apart. One week after the last injection, animals were given 50 consecutive active avoidance trials in a shuttle box. Animals treated with amphetamine exhibited a 50%, depletion of striatal dopamine and showed a slower learning curve, as evidenced by significantly fewer avoidances and a slower escape latency during trials 21-30. Both groups demonstrated a 90% avoidance rate by trials 41-50. A separate group of rats was treated as above and trained for several weeks on the active avoidance procedure. Haloperidol (0.01-0.10 mg/kg intraperitoneally) dose-dependently decreased avoidance number and increased avoidance and escape latency in both groups, an effect that was exaggerated in those animals previously treated with amphetamine. Finally, these animals were tested in the same apparatus using a passive avoidance procedure. The amphetamine treatment produced a significantly higher mean number of avoidances in this procedure compared to saline-treated animals during trials 1-20. These results suggest that the impairment in conditioned avoidance following amphetamine treatment is due to a motoric, rather than a cognitive deficit.

Effects of delta8 tetrahydrocannabinol (THC) on avoidance extinction in rats

Using a fixed behavioral test—resistance to extinction of avoidance responding in rats in the Baum box—the effects of delta8-THC were examined with the drug at various degrees of decomposition. Partially decomposed THC had no significant overall effect on avoidance-extinction responding. However, substantially decomposed THC produced significant extreme reactions in one group of rats, with some subjects showing virtually no extinction responding, whereas others displayed greatly increased responding. In Experiment 2, pure delta8-THC was found to significantly hasten extinction, but only if rats had never experienced the drug before (i.e., a tolerance effect was demonstrated). Drug dosage throughout was 5 mg/kg.

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.

The effects of dl-cathinone, d-amphetamine and cocaine on avoidance responding in rats and their interactions with haloperidol and methysergide

The effects of dl-cathinone ( dl-CAT), d-amphetamine ( d-A), and cocaine (COC) on conditioned shock avoidance responding and their interactions with haloperidol and methysergide on this behavior were studied in male Wistar rats. All three stimulants produced significant increases in intertrial interval (ITI) responding and in the number of avoidance responses and a decrease in avoidance latencies. These actions were antagonized by pretreatment with haloperidol (0.07 and 0.15 mg/kg, IP). Pretreatment with methysergide (1.0 and 2.0 mg/kg, IP) increased the effects of all three stimulants on ITI responding, but not on the other two parameters. These results suggest that the effects of these stimulants on avoidance responding may be mediated by dopaminergic systems. In addition, these stimulant-induced changes on ITI responding probably also involve actions on serotonergic systems.

Avoidance and ICSS behavioral models dissociate TL-99 and 3-PPP from dopamine receptor antagonists

The behavioral effects of the putative dopamine autoreceptor agonists, TL-99 and 3-PPP, were explored in animal procedures that reveal highly characteristic effects of neuroleptics currently in clinical use. Sidman avoidance responding in rats was not altered appreciably by doses up to 10 mg/kg TL-99 or 30 mg/kg 3-PPP. Higher doses of TL-99 attenuated Sidman avoidance performance in squirrel monkeys, although 3-PPP had no effect. Lever pressing for intracranial self-stimulation (ICSS) was attenuated in a dose-related fashion by TL-99 and 3-PPP, with relatively shallow dose-response relationships. A low dose of haloperidol (0.03 mg/kg) partly reversed the effects of 3-PPP (3 mg/kg) on lever pressing ICSS, but not those of TL-99 (3 mg/kg). Yohimbine (3 mg/kg) failed to alter the effects of TL-99 at a dose that abolished the suppresant effect of clonidine on ICSS. Analysis of within-session ICSS response decrement patterns indicated that TL-99 reduced ICSS to a greater extent towards the end of the session than during the first 5 min. No such within-session trend was produced by 3-PPP, suggesting that 3-PPP attenuates ICSS by virtue of a performance deficit. Similar conclusions were reached using a shuttlebox task that involved self-regulation of ICSS duration by rats. Therefore, the clinical profile of neuroleptics is unlikely to be mimicked precisely by 3-PPP or TL-99. Clinical trials of DA autoreceptor agonists for antipsychotic efficacy will indicate whether or not avoidance and ICSS behaviors are relevant to the detection of the intrinsic antipsychotic activity of drugs.

Feedback stimuli and the extinction of avoidance responding in rats.

Feedback stimuli and the extinction of avoidance responding in rats.

Effects of repeated administration of d-amphetamine on Sidman avoidance responding in rats.

The effects of repeated administration of d-amphetamine (0.5 mg/kg SC) on Sidman avoidance responding in rats were investigated. The response (lever-pressing) enhancing effect of d-amphetamine increased progressively after repeated administration. The change in behavior was more marked in the animals exposed to the avoidance situation during the period of the drug effect than in those given the drug after termination of each avoidance session. The present results suggest that the enhancing effect of d-amphetamine as demonstrated on Sidman avoidance responding in rats is dependent on the drug experience of the experimental animals and on the experimental situation to which the animals are exposed during the period of the drug effect.

The effects of dorsal bundle injections of 6-hydroxydopamine on avoidance responding in rats.

1 The effect of injection of 6-hydroxydopamine (6-OHDA) into the fibres of the dorsal noradrenergic bundle on acquisition, retention and extinction of active avoidance in rats were examined. 2 6-OHDA injections severely depleted noradrenaline in all forebrain areas assayed, with the interesting exception of the septum. No significant effect on dopamine concentrations in various forebrain regions was found. 3 Acquisition and retention of active avoidance was not altered by the lesion. Marked resistance to extinction was seen when the unconditioned stimulus (shock) was removed. 4 A comparison with work by other authors in which both forebrain noradrenaline and dopamine were depleted suggest that the alteration in extinction seen in both studies is a noradrenergic effect, whereas the deficits in acquisition and retention found previously are dopaminergic in origin.

Avoidance extinction in goldfish

Independent groups of goldfish trained to avoid shock in a shuttlebox situation were presented with several extinction procedures in which the relationships between the conditioned stimulus and shock were altered and/or response contingencies removed. Random shock presentations, equivalent to the number of shocks received during avoidance acquisition, resulted in response decrements similar to those obtained when the conditioned stimulus was presented alone. Pairing the conditioned stimulus with shock on every trial, however, served to maintain response levels. When response-contingent punishment was superimposed upon these Pavlovian pairings, performance was facilitated slightly although punishment alone resulted in somewhat faster response reduction than that produced by exposure only to the conditioned stimulus. Extinction of avoidance responding produced by exposure to the conditioned stimulus alone was dependent on the total duration of exposure and independent of both number of stimulus onsets and response prevention. These experiments demonstrated that, in general, the procedures used to reduce avoidance responding in rats were equally effective for goldfish, with one exception: the introduction of a Pavlovian contingency following avoidance acquisition, making the previously avoidable shock unavoidable, maintained response probabilities near previously established levels.

Effect of prestimulation on avoidance responding in rats, and hormonal dependence of the effect.

Rats were tested daily in a free-operant avoidance task and were found to make more avoidance responses in sessions preceded by a brief period of prestimulation than in control sessions. Footshock, air blast, and handling were effective sources of prestimulation for this effect. Further experiments showed that the effect of prestimulation depended on the presence of circulating mineralocorticoid and not on any other adrenal or pituitary hormone. Adrenalectomy, but not hypophysectomy, abolished the effect. The effect was also abolished in intact rats by maintaining them on saline drinking fluid, a procedure that inhibits mineralocorticoid production. In either adrenalectomized rats or intact, saline-maintained rats, injection of mineralocorticoid permitted the effect of prestimulation to reappear while leaving the nonprestimulated response rate unaffected.

Differentiation of escape and avoidance responding in rats.

Differentiation of escape and avoidance responding in rats.

Temporary improvement in shuttle-box performance of rats after repeated electroconvulsive shock treatment

Abstract Studies were conducted to determine the effect of repeated electroconvulsive shock (ECS) treatment on avoidance responding of rats which were poor performers in a two-way shuttle-box. Following 14–20 training sessions, ECS was administered twice daily for 5–8 days. After completion of the ECS treatments, the animals underwent further behavioral testing. The results may be summarized as follows: (1) repeated ECS treatment, without simultaneous training, produced a significant improvement in avoidance responding; (2) the improved performance could not be explained on the basis of spontaneous crossings in the shuttle-box; (3) the improved performance subsided by 72–96 hr after the last ECS; (4) the return to poor performance occurred spontaneously with the passage of time and was not dependent on relearning; (5) α-methyltyrosine pretreatment (50 or 100 mg/kg 2 hr before trials) did not alter the ECS-induced improvement of performance. At least two CNS pathways may be involved in shuttle-box performance, an adrenergic facilitatory system and a cholinergic inhibitory system. An appropriate change in activity (or excitability) of either or both systems could result in an improvement of shuttle-box performance. Although α-methyltyrosine failed to alter the ECS effect, these experiments do not justify elimination of an adrenergic mechanism. This temporary effect of ECS on shuttle-box performance does not involve memory consolidation.

Comparison of Two Techniques for Hastening Extinction of Avoidance-Responding in Rats

Response prevention (forced detention of the animal in the situation which it fears) and the shortening of the intertrial interval (massing of trials) are two techniques for hastening the extinction of avoidance responding in rats. Experiments wert conducted to compare the two techniques on two types of avoidance behavior: (1) a response which had been trained to a criterion of 10 consecutive avoidances (Exp. 1) and (2) a response which had been trained, extinguished, and then re-trained (Exp. 2). For both types of avoidance responding, shortening the Intertrial interval produced extinction in less time than did response prevention. A long period of response prevention was also effective in producing extinction.

Harmaline effects on tetrabenazine depression of avoidance responding in rats

Rats on a RS 40SS 20 shock avoidance schedule of reinforcement were administered tetrabenazine and harmaline both individually and combined in various time and dose sequences. The effects of harmaline on the tetrabenazine response were found to be both antagonistic and synergistic. Tetrabenazine alone elicited behavioral depression of avoidance responding in the rat. Harmaline pretreatment had an antagonistic effect on the tetrabenazine response producing an increase in the latency of depression (which sometimes included an initial period of behavioral excitation) followed by a synergistic increase in the duration of depression.