Recovery of delayed alternation in rats after lesions in medial frontal cortex and septum.

Two experiments using contingently reinforced T-maze alternation with 48 male Long-Evans and hooded rats found that (a) normal Ss, after achieving high accuracy in alternation with brief (0 sec) intertrial intervals (ITIs), dropped to chance levels with longer ITIs (90 sec) but reacquired effective alternation with additional practice; (b) small lesions in mediodorsal pregenual cortex had no effect on postoperative retention of alternation at either short or long ITIs; (c) however, small lesions in posterodorsal septum temporarily disrupted alternation at brief ITIs, whereas at long ITIs Ss chose randomly and never recovered; and (d) large lesions in medial frontal cortex disrupted retention of alternation at brief ITIs of 10 sec but significant recovery did occur with additional experience. Implications regarding task difficulty and locus of lesion for recovery of function are discussed. (22 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Temporal properties of gustatory spontaneous alternation in rats.

Describes 2 experiments in which female albino Sprague-Dawley rats (n = 24 each) drank a flavored solution for 1/2 hr. After a variable delay interval, Ss were allowed to choose for 15 min between the same solution and a differently flavored one. Ss drank more of the different solution after delays up to 4-6 hr. This result demonstrates spontaneous alternation for tastes, and confirms the long memory span previously observed in gustatory-visceral conditioning. (15 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Patterned (single) alternation in infant rats after combined or separate lesions of hippocampus and amygdala.

The role of the developing hippocampus and the amygdala on patterned (single) alternation (PA) in the infant rat was investigated in 4 experiments. In Exps 1 and 2, Ss were given 2 bilateral electrolytic hippocampal lesions or sham surgeries at 10 or 11 days of age and were trained 6 days later in a straight runway. In Exp 1, there were 120 trials in 1 day, with an 8-, a 15-, or a 30-s intertrial interval (ITI). PA learning occurred in lesion and sham Ss at the 8- and 15-s ITIs. In Exp 2, training was extended to 240 trials over 2 days, with a 30- or 60-s ITI. Sham and lesion Ss showed PA at the 30-s ITI, but the emergence of PA was delayed in the lesion pups at the 60-s ITI. In Exp 3, amygdaloid lesions had no effect on PA learning at the 8-s ITI. However, when Ss with hippocampal and amygdaloid lesions were trained at the 8-s ITI, the emergence of PA was delayed, and its size was reduced (Exp 4). Results argue for a role of the hippocampus in PA learning at long ITIs and suggest that, even in 16-day-old Ss exposed to an 8-s ITI, the combined hippocampal and amygdaloid lesion produces a deficit greater than either the hippocampal or the amygdaloid lesion. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Estrogen and estrogen-progesterone treatments counteract the effect of scopolamine on reinforced T-maze alternation in female rats.

Determined if steroid hormone treatments would attenuate the effect of the muscarinic receptor blocker scopolamine on a memory task. Ovariectomized rats were trained first to alternate for food reward between the arms of a T maze. Following training, Ss treated with scopolamine hydrobromide (0.2 mg/kg, ip) did not alternate correctly between the arms of the T maze and responded at chance levels. However, when estradiol benzoate (25 μg) was administered 72, 48, and 24 hrs before testing alone or in combination with progesterone (500 μg) administered 48 hrs before testing, Ss alternated successfully between the arms of the T maze following scopolamine administration. Results indicate that gonadal steroids can completely counteract the impairment of T maze performance induced by scopolamine in female rats. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Serotonergic and cholinergic involvement in habituation of activity and spontaneous alternation of rats in a maze.

Studied the effects of drug administration to 220 male Sprague-Dawley rats on spontaneous alternation (SA) in a -maze which Ss were permitted to freely explore for 8-min sessions. Results show that SA was not affected by administration of methysergide or the serotonin (5-HT) depletors DL-chloroamphetamine (PCA) and DL-p-chlorophenylalanine (PCPA). However, either LSD, or d-amphetamine in combination with methysergide, PCA, or PCPA interfered with SA. Scopolamine also disrupted SA, but pretreatment with 5-hydroxytryptophan or amphetamine blocked this action. Amphetamine reversal of the scopolamine-induced disruption of SA did not occur in Ss depleted of 5-HT or pretreated with methysergide. Amphetamine disrupted habituation of exploratory activity alone or after PCPA or PCA. PCPA or PCA alone did not affect habituation. Scopolamine interfered with habituation of activity. Methysergide caused an increase in the initial activity level, while LSD produced a dose-dependent decrease. (34 ref.) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Some effects of single alternation training of rats in a double runway.

Gave independent groups of male hooded rats (n = 30) either (a) single alternation (SA) of reward and nonreward in the 1st goal box of a double runway and 100% reward in the 2nd goal box, (b) concurrent SA in both goal boxes, (c) SA in the 1st goal box and no experience in the 2nd runway, or (d) random 50% reward in the 1st goal box accompanied by 100% reward in the 2nd goal box. SA training in the 1st or in both segments of the double runway yielded reliable SA patterning wherever such training occurred. Concurrent SA training in both segments yielded the fastest development of patterning. "Frustration effects" in the 2nd runway were consistently greater following SA in the 1st goal box than following random reward and nonreward. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Effects of scopolamine on spatial double alternation in rats.

Developed and tested a method for training spatial double alternation in 3 experiments, with a total of 4 male albino Wistar rats and 10 male albino Sprague-Dawley rats. Responding on different components of the sequence was controlled by different interoceptive and exteroceptive stimuli. This base line was used to compare the effects of scopolamine (.25-1 mg/kg) on the 2 sorts of cued responding in the same S. The 2 types of response did not differ appreciably in susceptibility to disruption by scopolamine. An analysis of errors showed that both switching and perseverative errors were increased by scopolamine, and that no lever preferences developed. An analysis of the various response sequences shows that in the same S, the probability of some sequences decreased consistently with increasing dose level, some sequences increased, and others showed an inverted -shaped function. (20 ref.) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Anxiolytic effects of cytotoxic hippocampal lesions in rats.

Rats with cytotoxic lesions of the hippocampus were given 3 anxiety tests: social interaction with a novel rat, the elevated zero-maze (a modification of the plus-maze), and hyponeophagia (eating familiar and novel foods in a novel place). Marked anxiolytic effects were seen in the social interaction and hyponeophagia tests, but not on the zero-maze. These results confirm and extend previous experiments that used traditional lesion techniques. The zero-maze result was consistent with other experiments using the plus-maze, in which intrahippocampal administrations of pharmacological agents were not anxiolytic, although variability in ethological tests may also be a factor. As the hyponeophagia test used an elevated apparatus, as in the zero- and plus-mazes, the lack of a lesion effect in the zero-maze was unlikely to have been due to an inability to relieve height-induced anxiety. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Pretraining effects on performance of rats with hippocampal lesions.

Investigated the role of pretraining factors in the overresponding observed on differential-reinforcement-of-low-rate (DRL) schedules following hippocampal lesions. 24 Long-Evans hooded rats divided into unoperated Ss and Ss with large or small hippocampal lesions were given 10 or 20 days of continuous reinforcement (CRF) pretraining before exposure to a DRL 20-sec schedule. Either large lesions or extended CRF pretraining resulted in only a transient elevation in response rates, while the unique combination of a large lesion and extended pretraining was required for persistent overresponding on DRL. It is concluded that the overresponding produced by hippocampal damage is not solely a function of loss of hippocampal tissue but depends upon unique training conditions for its appearance. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Effects of amphetamine, morphine and dizocilpine (MK-801) on spontaneous alternation in the 8-arm radial maze

The induction of psychomotor activation, behavioural sensitization and of perseverative behaviours, resulting in reduced behavioural variability, have been proposed to be common properties of drugs of abuse. The present investigation tested whether these drug effects could be measured using spontaneous alternation in an 8-arm radial maze. Behavioural effects of repeated treatment with amphetamine (2 and 4 mg/kg, i.p.), morphine (1.25 and 10 mg/kg, i.p.) and the non-competitive NMDA receptor antagonist, MK-801 (0.1 and 0.2 mg/kg, i.p.), on spontaneous alternation were evaluated in this paradigm. All drugs induced psychomotor activation. Sensitized as well as reduced locomotor activity could be observed after repeated treatment depending on drug and dose. Analysis of the sequences of arm entries revealed that all drugs induced perseverative locomotor patterns, but the pattern induced by amphetamine and morphine differed qualitatively from the pattern induced by MK-801.     

Impairment of spontaneous alternation behavior in sequential test procedures following mammillary body lesions in mice: Evidence for time-dependent interference-related memory deficits.

The experiments reported here examined the effects of either radio frequency or kainic acid lesions of the median mammillary nucleus (MM) on spatial spontaneous alternation (SA) in mice. Animals were tested in a T-maze with sessions of six to nine successive trials given at varying intertrial intervals (ITIs). In the first experiment, conducted with an ITI of 30 s, damaged animals exhibited normal rates of SA on the second trial of the session but were progressively impaired on subsequent trials compared with controls. This finding was interpreted as an increased vulnerability to proactive interference. The second experiment was designed to investigate the effect of the ITI, and the results indicated that the previously observed impairment was completely suppressed by reducing the ITI from 30 s to 5 s. In order to further test our interference hypothesis, a third experiment was designed to investigate whether providing the animals with an extrinsic cue on one trial (5th) would increase the rate of SA on the subsequent (6th) trial (release from interference). Unexpectedly, results from this experiment showed that performance dramatically improved as soon as the cue was provided (i.e., on the 5th trial). (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Suppressive and enhancing effects of footshock on food-reinforced operant responding following septal lesions in rats.

Measured effect of septal lesions on suppression of an intermittently food-reinforced lever press by contingent and noncontingent footshock, using a total of 48 experimentally naive male hooded Lister rats in 2 experiments. Ss with septal damage maintained higher response rates than did intact Ss under both contingent and noncontingent shock. Furthermore, the difference in suppression produced by the contingent and noncontingent conditions was approximately the same for the experimental Ss and controls. In Exp II performance was measured during counter-conditioning in which the correlation between contingent shock and positive reinforcement was varied. Ss with septal lesions responded at higher rates than did controls. When only reinforced responses were punished, this lesion-induced elevation represented an increase above baseline performance without punishment. This finding suggests that the effect of septal damage on appetitive instrumental performance cannot be due solely to a deficit in response inhibition. (27 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Nucleus basalis lesions suppress spike and wave discharges in rats with spontaneous absence-epilepsy

Cholinergic drugs were shown to affect spike and wave discharges in a selected strain of Wistar rats with generalized non-convulsive absence epilepsy, named GAERS (Genetic Absence Epilepsy Rats from Strasbourg). The involvement of cholinergic transmission from the nucleus basalis in the control of absence seizures in GAERS was investigated in the present study, by examining the effects of unilateral excitotoxic lesions of this nucleus on the occurrence of spike-wave discharges. Ibotenate (0.01 M) and quisqualate (0.03 and 0.06 M)-induced lesions of the nucleus basalis suppressed spike-wave discharges in the cortex ipsilateral to the lesion. The suppression was associated with a disappearance of both acetylcholinesterase-fibres in the cerebral cortex and choline acetyltransferase immunopositive neurons within the nucleus basalis. Concomitantly, the background electroencephalographic activity was slowed. These results suggest that cholinergic innervation of the cerebral cortex by the nucleus basalis is involved in the occurrence of generalized non-convulsive seizures, in relation to the control of cortical activation.     

Septal infusions of the hyperpolarization-activated cyclic nucleotide-gated channel (HCN-channel) blocker ZD7288 impair spontaneous alternation but not inhibitory avoidance.

Blockade of septal hyperpolarization-activated cyclic nucleotide-gated channels (HCN) impairs hippocampal theta, an effect that would be expected to impair memory. To test this hypothesis, the present experiments determined whether septal infusions of the selective HCN channel blocker ZD7288 would impair performance on two memory tasks that involve the septo-hippocampal system: spontaneous alternation (SA) and continuous multiple inhibitory avoidance (CMIA). Fifteen minutes prior to assessing SA or CMIA, different groups of male Sprague-Dawley rats were given septal infusions of saline or ZD7288 (0.2, 0.6 or 1.5 μg/0.5 μ1). Septal infusions of ZD7288 impaired SA in a dose-dependent manner; the same infusions did not affect CMIA acquisition or retention. These results appear to be the first demonstration that HCN channels in the medial septum influence memory. Specifically, they suggest that septal HCN channels play a permissive role in spatial working memory, but do not influence emotional long-term memory. Given that these channels are preferentially located on GABA septo-hippocampal projection neurons, the present data provide further evidence that these projection neurons are involved in memory. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Differential effects of unilateral and bilateral caudate lesions on side preferences and timing behavior in rats.

Trained 24 female Sprague-Dawley rats to barpress on a DRL-16 sec schedule for water reinforcement. Ss were allowed to barpress on either of 2 levers (left and right). All Ss showed consistent side preferences. For the nonsignaled condition, normal rates were related to the strength of side preferences; lower rates and better timing performance were significantly correlated with greater preferences. Unilateral lesions in the caudate nucleus ipsilateral to side preferences facilitated performance during nonsignaled test sessions and increased side preferences during both. Unilateral lesions contralateral to side preferences impaired performance during nonsignaled test sessions and decreased side preferences during all sessions. Bilateral lesions transiently depressed response rates without significantly affecting timing performance or side preferences. It is suggested that side preferences are intimately involved in the control of behavior by internal stimuli and that an inherent asymmetry in nigrostriatal function underlies side preferences; the effect of a unilateral striatal lesion will depend on whether the lesion is placed in the more or less active striatum. (22 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Behavioral effects of amphetamine in rats with lesions in the corpus striatum.

Conducted 5 experiments, using a total of 132 male albino Sprague-Dawley rats. Lesions in the ventral striatum lowered forebrain dopamine and impaired avoidance behavior more severely than comparable lesions in the dorsal striatum. Ventral striatal damage also antagonized the effects of amphetamine on stereotyped behavior and on intertrial activity. Lesions in the dorsal striatum did not modify the effect of amphetamine in these tests. Neither dorsal nor ventral striatal lesions significantly depleted forebrain norepinephrine, and both failed to affect the facilitatory effects of amphetamine on exploratory activity in an open field. These observations support the hypothesis that some but not all of the behavioral effects of amphetamine may be due to the drug's action on dopaminergic components of the striatum. (32 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Approach and withdrawal analysis of the effects of hypothalamic stimulation and lesions in rats.

Identified "purely" rewarding lateral hypothalamic and "purely" aversive medial hypothalamic electrodes in a paradigm in which Charles River male rats both initiated and terminated hypothalamic stimulation. Ss were then given a series of tests designed to assess the effects of brain stimulation on approach and withdrawal behaviors. Lateral hypothalamic stimulation facilitated approach behaviors and suppressed withdrawal behaviors, whereas medial hypothalamic stimulation produced largely the opposite effects. No serious motor deficits due to stimulation were detected with either type of electrode. In a 2nd experiment, the approach–withdrawal effects of bilateral lateral hypothalamic lesions were tested and found to suppress approach behaviors and facilitate withdrawal behaviors. Other neurological examinations revealed motor deficits, but these did not account for the specific pattern of results observed on the approach–withdrawal test. These approach–withdrawal phenomena are interpreted in terms of altering a natural balance between approach and withdrawal behavior facilitating systems in the lateral and medial hypothalamus, respectively. (43 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Ventromedial septal lesions in rats reduce the effects of inescapable shock on escape performance and analgesia.

In 2 experiments with 104 male Sprague-Dawley rats, lesions of the ventromedial septum (VMS) reduced or eliminated several effects of exposure to inescapable shock, but lesions of the dorsolateral septum did not. Exp I demonstrated that VMS lesions reduced the loss in body weight produced by inescapable shock and eliminated the subsequent (24 hrs later) interference with escape performance (learned helplessness). Exp II demonstrated that VMS lesions reduced the analgesia that occurs immediately following inescapable shock and the analgesia reinstated by exposure to escapable shock 24 hrs later. Findings indicate that VMS lesions reduce several responses to inescapable shock and suggest the possibility that all of these effects may reflect a unitary deficit. It is hypothesized that VMS lesions reduce these effects of exposure to inescapable shock either by reducing the ability of the rats to learn that their responses and shocks were uncorrelated or by reducing the emotional impact of this lack of correlation. (52 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Effect of preinduction of heat-shock proteins on acetic acid-induced small intestinal lesions in rats

Bowel dysfunction such as irritable bowel syndrome caused by stress is well described. Previous reports suggest that stress is known to cause the release of endogenous substances such as catecholamine, beta-endorphine, 5-hydroxytryptamine, corticotropin-releasing factor, and thyrotropin-releasing hormone (TRH). However, the role played by these neurohormonal mediators in bowel dysfunction under stress conditions is not well known. We investigated the influence of water-immersion stress or TRH administration on the expression of 60-kDa, 72-kDa, and 90-kDa heat-shock proteins (HSP60, HSP72, and HSP90, respectively) in rat small intestinal mucosa by Western blot and immunohistochemical analyses. The cytoprotective function of preinduced HSPs on experimentally induced mucosal damage also was studied. In order to investigate the influence of preinduction of HSP60 on small intestinal damage, the small intestinal lumen was perfused with 1.5% acetic acid 1 ml/min for 15 min with or without pretreatment with water-immersion stress or TRH administration. Expression of HSP60 was significantly increased by water-immersion stress or TRH administration in the small intestinal mucosa, whereas HSP72 and HSP90 did not increase. Interestingly, expression of this protein showed the biphasic peak pattern after water-immersion stress or TRH administration. Each peak was observed 3-6 hr and 21-24 hr after the initiation of water-immersion stress or TRH administration. Immunohistochemical study also showed a significant increment of HSP60 in both the cytoplasm and nuclei of the small intestinal mucosal cells. No histopathologic alteration was observed in rat small intestinal mucosa after each treatment. Small intestinal damage caused by 1.5% acetic acid perfusion was not influenced by preinduction of HSP60. We demonstrated that water-immersion stress or TRH administration specifically induced HSP60, although preinduction of this protein did not show a cytoprotective function in the small intestinal mucosa.