Effect of nucleus basalis magnocellularis cholinergic lesions on fear-like and anxiety-like behavior.

Previous research has suggested that cholinergic neurons in the nucleus basalis magnocellularis and substantia innominata (NBM/SI) may be important in mediating aversive states. The authors investigated the effect of NBM/SI cholinergic lesions, induced with 192 IgG saporin, on behavioral measures of aversive states in rats. Behavior in the elevated plus maze and behavioral suppression induced by 2 fear-conditioned stimuli, a tone and a light, were evaluated. Lesions had no effect on any measures in the elevated plus maze but attenuated operant suppression induced by the light and attenuated freezing induced by the tone, though this last effect was not statistically significant. The results of the study suggest that NBM/SI cholinergic neurons may be important in mediating selective aspects of aversive states. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Medial Septal Lesions Mimic Effects of Both Selective Dorsal and Ventral Hippocampal Lesions.

Electrolytic medial septal (MS) lesions, which depleted acetylcholinesterase staining in both dorsal and ventral hippocampus, produced a constellation of behaviors, combining aspects of both selective dorsal and ventral hippocampal lesion effects. MS lesions impaired spatial working memory on the T maze, thus resembling the effects of dorsal hippocampal lesions. In addition, MS lesions reduced anxiety during successive alleys (a modified form of the elevated plus-maze), social interaction, and hyponeophagia tests. MS lesions also reduced postshock freezing. These effects more closely resemble those of ventral hippocampal lesions. Therefore, the effects of electrolytic MS lesions derive from the resulting combined deafferentation of dorsal and ventral hippocampal regions, suggesting that previously reported effects of cytotoxic dorsal hippocampal lesions are unlikely to be due to a demyelination of fibers of passage coursing through the septal pole. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Modulation of Different States of Anxiety-Like Behavior by Chronic Stress.

Recent studies have identified putative cellular correlates of stress-induced amygdalar plasticity underlying anxiety-like behavior. Chronic immobilization stress (CIS), but not chronic unpredictable stress (CUS), has been reported to induce dendritic remodeling in the basolateral amygdala (BLA). The BLA is also important for consolidation of anxiety in the elevated plus-maze, which is manifested as increased open-arm avoidance on reexposure to the maze. The authors found that CIS, unlike CUS, facilitated anxiety-like behavior in the plus-maze, and this occluded further increase in anxiety when CIS rats were reexposed to the maze 72 hr after the first trial. However, both CUS and control rats exhibited consolidation between trials. Thus, consolidation of anxiety may share common cellular mechanisms that also underlie chronic stress-induced structural plasticity in the amygdala. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Disconnection of the amygdala central nucleus and the substantia innominata/nucleus basalis magnocellularis disrupts performance in a sustained attention task.

The basal forebrain cholinergic system is broadly implicated in the regulation of attention. Disruptions in the function of this system produce impairments in many attentional functions, including the performance of well-learned responses under increased attentional load and the surprise-induced enhancement of learning rate. Similarly, lesions of the amygdala central nucleus (CeA) have been found to impair attentional function in some circumstances. In the present article, the effects of lesions that disconnected CeA from the cholinergic substantia innominata/nucleus basalis magnocellularis (SI/nBM) on performance are examined in a modified 5-choice serial reaction time (5CSRT) task, thought to assess selective or sustained attention. The lesions impaired performance under conditions of increased attentional load, suggesting that a circuit that includes CeA and SI/nBM regulates these aspects of attention. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Effects of bed nucleus of the stria terminalis lesions on conditioned anxiety: Aversive conditioning with long-duration conditional stimuli and reinstatement of extinguished fear.

Four experiments investigated the effects of lesions of the bed nucleus of the stria terminalis (BNST) on conditioned fear and anxiety. Though BNST lesions did not disrupt fear conditioning with a short-duration conditional stimulus (CS; Experiments 1 and 3), the lesion attenuated conditioning with a longer duration CS (Experiments 1 and 2). Experiment 3 found that lesions attenuated reinstatement of extinguished fear, which relies on contextual conditioning. Experiment 4 confirmed that the lesion reduced unconditioned anxiety in an elevated zero maze. The authors suggest that long-duration CSs, whether explicit cues or contexts, evoke anxiety conditioned responses, which are dissociable from fear responses to shorter CSs. Results are consistent with behavioral and anatomical distinctions between fear and anxiety and with a behavior-systems view of defensive conditioning. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Electrolytic lesions of the nucleus accumbens enhance locomotor sensitization to nicotine in rats.

Electrolytic lesions of the medial core of the nucleus accumbens (NAc) in male Long-Evans rats increased spontaneous locomotion, enhanced the locomotor stimulating effect of acute 5.0 mg/kg cocaine, enhanced the development and subsequent expression of locomotor sensitization produced by repeated injections of 0.4 mg/kg nicotine but not 7.5 mg/kg cocaine, and enhanced the expression of conditioned locomotion. Given that 6-hydroxydopamine lesions of the NAc typically have effects on locomotor-related processes that are opposite of those produced by electrolytic and excitotoxic lesions, these data are consistent with a hypothesis that the NAc output, especially from the core, inhibits a variety of such processes and that the DA input to the NAc enhances these processes by inhibiting this inhibitory output. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Mild Topographical Memory Impairment Following Crossed Unilateral Lesions of the Mediodorsal Thalamic Nucleus and the Inferotemporal Cortex.

Monkeys with crossed unilateral lesions of the dorsomedial thalamus and contralateral ablations of the inferotemporal cortex were mildly impaired on acquisition and retention of visual conditional tasks requiring the integration of information about objects and their positions in space. They were not impaired on other conditional and nonconditional tasks. This impairment pattern resembles, qualitatively, that found following crossed unilateral lesions of the anterior thalamus and the inferotemporal cortex or bilateral lesions of the anterior and mediodorsal thalamic nuclei. Although the flow of visual information from the inferotemporal cortex through the hippocampal-fornix-anterior thalamic circuit plays a major part in memory for objects in places, the flow of information between inferotemporal cortex and mediodorsal thalamus, possibly by means of the frontal cortex, also makes some contribution. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Path integration and lesions within the head direction cell circuit: Comparison between the roles of the anterodorsal thalamus and dorsal tegmental nucleus.

Experiments were designed to determine whether 2 regions of the head direction cell circuit, the anterodorsal thalamic nucleus (ADN) and the dorsal tegmental nucleus (DTN), contribute to navigation. Rats were trained to perform a food-carrying task with and without blindfolds prior to receiving sham lesions or bilateral lesions of the ADN or DTN. ADN-lesioned rats were mildly impaired in both versions of the task. DTN-lesioned rats, however, were severely impaired and showed reduced heading accuracy in both task versions. These findings suggest that although both the DTN and ADN contribute to navigation based on path integration and landmarks, disruption of the head direction cell circuit at the level of the DTN has a significantly greater effect on spatial behavior than lesions of the ADN. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Inhibitory learning tests of conditioned stimulus associability in rats with lesions of the amygdala central nucleus.

Normal rats showed faster inhibitory learning about a light conditioned stimulus (CS) if it had previously been an inconsistent predictor of a tone CS than if it had been a consistent predictor of the tone. In contrast, the inhibitory learning of rats with ibotenic acid lesions of the amygdala central nucleus (CN) was unaffected by the prior predictive value of the light. These results support claims that the CN is critical to surprise-induced enhancement of attentional processing of CSs. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Parabrachial nucleus lesions block taste and attenuate flavor preference and aversion conditioning in rats.

Rats with ibotenic acid lesions of the parabrachial nucleus (PBN) failed to learn a taste aversion induced by lithium chloride (LiCl) toxicosis. The same rats also did not learn to prefer a taste that was paired with intragastric (IG) carbohydrate infusions during 22 hr/day trials. The PBN-lesioned rats did learn to prefer a flavor (odor?+?taste) paired with the IG carbohydrate infusions over a different flavor paired with IG water. The PBN-lesioned rats also learned to avoid a flavor paired with IG LiCl infusions during 22 hr/day trials. The flavor preference and aversion, however, were less pronounced than those displayed by control rats. These data indicate that the PBN is essential for forming orosensory-viscerosensory associations when taste is the primary cue but is less critical when more complex flavor cues are available. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Lesions of the dorsal hippocampus or parietal cortex differentially affect spatial information processing.

The present experiments used 2 versions of a modified Hebb-Williams maze to test the role of the dorsal hippocampus (dHip) and parietal cortex (PC) in processing allocentric and egocentric space during acquisition and retention. Bilateral lesions were made to either the dHip or PC before maze testing (acquisition) or after maze testing (retention). The results indicate that lesions of the dHip impair allocentric maze acquisition, whereas lesions of the PC impair egocentric maze acquisition. During retention, lesions of the PC produced a significant impairment on both maze versions, whereas lesions of the dHip produced short-lived, transient impairments on both maze versions. These results suggest that during acquisition, the hippocampus and PC process spatial information in parallel; however, long-term retention of spatial information requires the PC with the dHIP as necessary for retrieval and/or access but not necessarily storage. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Lesions of the nucleus accumbens in rats reduce opiate reward but do not alter context-specific opiate tolerance.

Bilateral electrolytic lesions of the nucleus accumbens in rats eliminated the capacity of 10 mg/kg morphine to produce a conditioned place preference (Experiment 1). However, these lesions did not alter the capacity to establish context-specific tolerance to the analgesic effects of 5 mg/kg of morphine (Experiment 2). This latter finding indicates that rats with nucleus accumbens lesions are not impaired in associating the effects of morphine with a particular location. Thus, the failure of morphine to produce a conditioned place preference in these lesioned rats probably cannot be attributed to an inability to associate the effects of morphine with a particular chamber, i.e., the initially nonpreferred chamber. Rather, morphine may fail to establish a conditioned place preference in these rats because nucleus accumbens lesions disrupt a pathway that is critical in mediating the rewarding effects of opiates. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Effects of Hippocampus and Medial Caudate Nucleus Lesions on Memory for Direction Information in Rats.

A delayed matching-to-sample task was designed to assess memory for direction information in rats. During the study phase, rats traversed a maze arm oriented in 1 of 3 directions. After a delay period, a test phase was presented that required a choice between the study phase direction and a foil direction. Once rats reached a learning criterion, probe trials suggested that normal rats favor the use of direction, rather than turning response, information and use vestibular feedback. Rats were then given hippocampus, medial caudate nucleus (MCN), or cortical control lesions. Unlike control rats, those with hippocampus and MCN lesions exhibited marked impairments when retested. However, all rats were able to learn a direction discrimination task. These results suggest that the hippocampus and MCN support processes associated with short-term memory for direction information. (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)     

Increase of locomotor activity underlying the behavioral disinhibition in Tg2576 mice.

The transgenic Tg2576 mouse is a widely used animal model that develops some of the cognitive and neuropathological deteriorations observed in patients suffering Alzheimer's disease. The authors investigated 9-month-old Tg2576 mice with respect to behavioral and endocrinological (hypothalamic- pituitary-adrenal [HPA] axis activity) parameters. The locomotor activity test revealed that Tg2576 mice moved almost twice as much as controls. Tg2576 mice spent significantly more time visiting the open arms and performed more entries into these open arms than did controls. However, the amount of time that Tg2576 mice remained in each entry to the open arm was similar to that of controls, and the number of arm entries correlated positively to locomotor activity. In the forced swimming test, Tg2576 mice showed a significant decrease in immobility time, which correlated negatively to locomotor activity. Parameters of the HPA axis, such as plasma level of corticosterone, adrenal gland weight, and noradrenaline or adrenaline release, did not differ between controls and Tg2576 mice. These data suggest that the disinhibitory behavior of Tg2576 mice seems to be related to increased locomotor activity but not to any disturbance of the HPA axis. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Selective serotonin receptor stimulation of the medial nucleus accumbens causes differential effects on food intake and locomotion.

Substantial evidence suggests that pharmacological manipulations of neural serotonin pathways influence ingestive behaviors. Despite the known role of the nucleus accumbens in directing appetitive and consummatory behavior, there has been little examination of the influences that serotonin receptors may play in modulating feeding within nucleus accumbens circuitry. In these experiments, the authors examined the effects of bilateral nucleus accumbens infusions of the 5-HT1/7 receptor agonist 5-CT (at 0.0, 0.5, 1.0, or 4.0 μg/0.5 μl/side), the 5-HT? receptor agonist EMD 386088 (at 0.0, 1.0, and 4.0 μg/0.5 μl/side), or the 5-HT2C preferential agonist RO 60–0175 (at 0.0, 2.0, or 5.0 μg/0.5 μl/side) on food intake and locomotor activity in the rat. Intra-accumbens infusions of 5-CT caused a dose-dependent reduction of food intake and rearing behavior, both in food-restricted animals given 2-hr free access to Purina Protab RMH 3000 Chow, as well as in nondeprived rats offered 2-hr access to a highly palatable fat/sucrose diet. In contrast, stimulation of 5-HT? receptors with EMD 386088 caused a dose-dependent increase of intake under both feeding conditions, without affecting measures of locomotion. Infusions of the moderately selective 5-HT2C receptor agonist RO 60–0175 had no effects on feeding or locomotor measures in food-restricted animals, but did reduce intake of the fat/sucrose in nonrestricted animals at the 2.0 μg, but not the 5.0 μg dose. Intra-accumbens infusions of selective antagonists for the 5-HT? (SB 269970), 5-HT? (SB 252585), and 5-HT2C (RS 102221) receptors did not affect locomotion, and demonstrated no lasting changes in feeding for any of the groups tested. These data are the first to suggest that the activation of different serotonin receptor subtypes within the feeding circuitry of the medial nucleus accumbens differentially influence consummatory behavior. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Inactivation of the median raphe nucleus increases intake of sucrose solutions: A microstructural analysis.

Previous studies have shown that microinjections of the GABA-A agonist muscimol into the median raphe nucleus (MR) result in large increases in the intake of solid foods. In the current study, we used microstructural techniques to characterize the effects of intra-MR muscimol injections on the consumption of either a 0.05 M or a 0.29 M sucrose solution. After injections of either saline or muscimol, animals consumed more of the 0.29 M than the 0.05 M solution, an effect which resulted primarily from increases in the initial rate of consumption with no change in the rate at which licking decayed across the test session. In contrast, intra-MR muscimol injections had little effect on the initial licking rate, but greatly increased meal duration, indicating that this treatment affected ingestion in a different way than did altering the sucrose concentration. Muscimol injections produced a significantly larger increase in the intake of the 0.29 M than of the 0.05 M solution. Intra-MR muscimol injections did not alter the within burst rate of licking, suggesting that they did not affect the functioning of the licking pattern generator. In contrast, these injections did increase the number of licks contained within “clusters,” that is groups of licks separated from each other by intervals of more than 0.5 sec. These findings show that inactivation of the MR produces a powerful effect on the intake of liquid diets, and that the nature of this effect is different from that produced here by changes in sucrose concentration and from those reported after pharmacological manipulations of a number of other brain systems. We additionally discuss several theoretical issues arising in the interpretation of microstructural data. (PsycINFO Database Record (c) 2011 APA, all rights reserved)     

A differential involvement of the shell and core subterritories of the nucleus accumbens of the rats in memory processes.

The role of the core and the shell subterritories of the nucleus accumbens in conditioned freezing and spatial learning was investigated by means of selective N-methyl-D-aspartate lesions. Shell-lesioned rats showed reduced conditioned freezing to context and a tendency toward reduced freezing to the discrete stimulus compared with controls. However, lesions of the core did not modify the freezing response either to the context or to the discrete stimuli. Although spatial memory, as assessed by a water-maze paradigm, was not disrupted by the lesions, in a 4-arm baited, 4-arm unbaited radial-arm maze paradigm, the shell-lesioned rats showed selective deficits in working memory, but not in reference memory. In contrast, core-lesioned rats showed no memory deficits. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Entorhinal cortex lesions disrupt the transition between the use of intra- and extramaze cues for navigation in the water maze.

[Correction Notice: An erratum for this article was reported in Vol 117(5) of Behavioral Neuroscience (see record 2007-16848-001). The definitions "Present = intramaze landmark present during Stage 2" and "Absent = intramaze landmark absent during Stage 2" appear incorrectly in the caption to Figure 3. These terms and definitions should appear in the caption to Figure 4.] This study with rats examined the effects of excitotoxic lesions to the entorhinal cortex (EC) and hippocampus (HPC) on using extramaze and intramaze cues to navigate to a hidden platform in a water maze. HPC lesions resulted in a disruption to the use of extramaze cues, but not intramaze cues, whereas EC lesions had no effect on the use of these cues when they were encountered for the fast time. However, prior navigation training in which 1 type of cue was relevant disrupted navigation with the other type in rats with EC lesions. Results show that the EC contributes to the processing of spatial information, but that this contribution is most apparent when there is a conflict between 2 sources of navigational cues in the water maze. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Effects of ibotenic acid lesions of the nucleus accumbens on paced mating behavior in the female rat.

The present study investigated the role of the nucleus accumbens (NAcc) in paced mating behavior in female rats. A sexually receptive female rat will approach and withdraw from a sexually active male, thereby controlling the timing of the receipt of sexual stimulation (e.g., mounts, intromissions, ejaculations). In this study, ibotenic acid lesions in the NAcc core increased the likelihood that a female rat would withdraw from a male rat after a mount but did not affect contact return latency or sexual receptivity. lbotenic acid lesions in the NAcc shell did not affect paced mating behavior or sexual receptivity. The results suggest that the NAcc core plays a role in suppressing withdrawal behavior in response to less intense mating stimulation. (PsycINFO Database Record (c) 2010 APA, all rights reserved)