The acetylcholine, GABA, glutamate triangle in the rat forebrain

The present overview demonstrates that stress, fear, novelty, and learning processes are associated with arousal and increases of extracellular levels of cortical and hippocampal ACh, independently of increases of motor activity. Forebrain cholinergic systems appears to be regulated by GABAergic and glutamatergic inputs. However, several other neurotransmitter systems play a role.     

Serial analysis of the effects of methimazole therapy on circulating B cell subsets in Graves'' disease

Acetylcholine (ACh) systems have been widely shown to be important for memory. In particular, ACh hippocampal neurons are critical for memory formation, though ACh innervation of other areas such as the nucleus accumbens may also be important. There has also been increasing interest in ACh and dopaminergic (DA) interactions with regard to short-term spatial memory. In a series of studies, we have found that ACh and DA agonists and antagonists given systemically interact to influence memory. The critical neural loci of these interactions are not currently known. In the present study, we used local infusion techniques to examine the role of ACh and DA transmitter systems in the nucleus accumbens and the ventral hippocampus on radial-arm maze (RAM) working memory performance. Into the nucleus accumbens of rats, we infused the nicotinic ACh agonist nicotine, the nicotinic ACh antagonist mecamylamine, the DA agonist apomorphine, or the DA antagonist haloperidol. Into the ventral hippocampus, we infused nicotine, mecamylamine, the muscarinic ACh agonist pilocarpine, or the muscarinic ACh antagonist, scopolamine. The nicotinic ACh and DA interaction was tested by a hippocampal infusion of mecamylamine alone or together with the DA D2 agonist quinpirole given via subcutaneous injection. The results confirmed that both nicotinic and muscarinic ACh receptors in the ventral hippocampus play a significant role in spatial working memory. Blockade of either nicotinic or muscarinic ACh receptors caused significant impairments in RAM choice accuracy. However, infusion of either nicotinic or muscarinic agonists failed to improve choice accuracy. The interaction of DA D2 systems in different with hippocampal nicotinic blockade than with general nicotinic blockade. Systemic administration of quinpirole potentiated the amnestic effect of mecamylamine infused into the ventral hippocampus, whereas it was previously found to reverse the amnestic effect of systemically administered mecamylamine. In contrast to the significant effects of mecamylamine in the hippocampus, no effects were found after infusion into the nucleus accumbens. Nicotine also was not found to have a significant effect on memory after intra-accumbens infusion. Neither the DA agonist apomorphine nor the DA antagonist haloperidol had a significant effect on memory after infusion into the nucleus accumbens. This study provides support for the involvement of nicotinic and muscarinic receptors in the ventral hippocampus in memory function. Ventral hippocampal nicotinic systems have significant interactions with D2 systems, but these differ from their systemic interactions. In contrast, nicotinic ACh and DA systems in the nucleus accumbens were not found in the current study to be important for working memory performance in the RAM.     

Beneficial effect of low-dose mianserin on fluvoxamine-induced akathisia in an obsessive-compulsive patient

This study employed in vivo microdialysis in awake, freely-moving Sprague-Dawley rats to examine acetylcholine (ACh) release in the dorsal hippocampus at 14 days following lateral controlled cortical impact. Extracellular levels of ACh were measured prior to and after an intraperitoneal administration of scopolamine (1 mg/kg), which evokes ACh release by blocking autoreceptors. At 14 days post injury there were no differences in basal ACh levels. However, injury produced a significant reduction in scopolamine-evoked ACh release. The data suggest that cholinergic neurotransmission remains chronically compromised, and thus may contribute to previously documented post traumatic spatial memory deficits.     

Activation of non-NMDA receptors stimulates acetylcholine and GABA release from dorsal hippocampus: a microdialysis study in the rat

The effect of the non-N-methyl-D-aspartate (NMDA) agonists (RS)-alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) and quisqualate (QUIS) on the release of acetylcholine (ACh), gamma-amino butyric acid (GABA), aspartate (Asp) and glutamate (Glu) from the hippocampus of freely moving rats was studied by transversal microdialysis. Intracerebroventricular (i.c.v.) administration of the non-NMDA receptor agonist AMPA (0.5 nmol) enhanced (by about 200%) ACh release from the hippocampus. The effect of AMPA was completely antagonized by 6-nitro-7-sulphamoyl-benz(f)quinoxaline-2,3-dione (NBQX; 2 nmol, i.c.v). No effect was seen when AMPA was perfused through the septum. However, AMPA (200 microM) locally applied to the hippocampus, increased (by about 200%) ACh release. QUIS (200 microM) applied locally to the hippocampus produced a long-lasting increase in the release of ACh (by about 215%) and GABA (by about 460%). Local infusion of tetrodotoxin (1 microM) decreased ACh and GABA basal extracellular levels, and abolished the QUIS-induced increase in ACh and GABA. Our results demonstrate that non-NMDA glutamatergic receptors in the hippocampus regulate hippocampal release of GABA and ACh.     

Odor modulation of ventral scent gland marking in the Mongolian gerbil.

In an experiment with 18 male and 18 female Mongolian gerbils, gerbil odors were allowed to accumulate in individual home cages for several months to provide stable olfactory stimuli that might modulate the number of ventral scent gland marks produced by the Ss. Male marking levels for most test conditions were 2–3 times larger than those in females, although, the relative patterns of responsiveness to particular odors were similar in both sexes. The number of scent marks in home cages was significantly smaller than the number obtained in clean cages. Marking levels in the home cages of other Ss were substantially higher than those seen in the test S's own cage and were maximal in the home cages of other males. Behaviorally receptive females marked at significantly higher levels in home, clean, and conspecific cages than did nonreceptive females. Conspecific urine odors, especially those from females, increased marking levels significantly over those obtained in home cages. In males, home cage marking was significantly enhanced by the presence of a female. Both sexes showed significant reductions in marking levels in another's cage if the resident was present. Results suggest that scent-marking like other olfactory guided behaviors and odor preferences, is context-specific. (36 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

The influence of photoperiod and sex on lipopolysaccharide-induced hypoactivity and behavioral tolerance development in meadow voles (Microtus pennsylvanicus)

Lipopolysaccharide (LPS), the minimal immunogenic component of Gram-negative bacteria, is released during infection and causes a variety of sickness behaviors including decreased locomotor activity. This study considered how photoperiod and sex influence the effects of LPS in the meadow vole, Microtus pennsylvanicus. Male and female voles were housed under either reproductively stimulatory (long day: 16 h) or inhibitory (short day: 8 h) photoperiods. On Days 1 and 8, voles were injected with LPS (200 microg/kg, i.p.) or saline vehicle and locomotor activity was assessed 2 h later in an automated open field for 1 h. The first exposure to LPS caused significant decrements in locomotor activity in all LPS-treated groups, regardless of photoperiod or sex. On Day 8, both short day males and females exhibited behavioral tolerance to LPS, no longer displaying significant activity decrements. In contrast, long day females reinjected with LPS on Day 8 still exhibited significant hypoactivity on all locomotor measures. Similarly, long day males also appeared to exhibit a sustained expression of sickness behaviors on Day 8. In long day females, higher circulating progesterone levels were associated with an attenuated rate of tolerance formation to LPS. The present findings support the winter immunoenhancement hypothesis, which states that small mammals which undergo severe seasonal fluctuations undergo compromised immune functioning during the breeding season, and further indicate a potential role for progesterone in modulating these seasonal immune fluctuations in females.     

DNA-protein interactions in the proximal zeta-globin promoter: identification of novel CCACCC- and CCAAT-binding proteins

The present study assessed whether prenatal androgen and estrogen exposure affected adult spatial learning and hippocampal morphology. Water maze performance, the CA1 and CA3 pyramidal cell field, and the dentate gyrus-granule cell layer (DG-GCL) morphology were assessed at adulthood (70+ days of age) in males, females, androgen-treated (testosterone propionate, TP, or dihydrotestosterone propionate, DHTP) females (2-4 mg/day), estradiol benzoate (EB)-treated females (100 microgram/day), and males treated with the antiandrogen flutamide (8 mg/day). Pregnant rats were injected daily (sc) between Embryonic Day 16 and birth; all pups were delivered by cesarean section. Flutamide-treated males were castrated upon delivery, and adult castrates were used to control for activational effects. Steroid-sensitive sex differences were observed in water maze performance in favor of males. Males had larger CA1 and CA3 pyramidal cell field volumes and soma sizes than females, which were feminized with flutamide treatment. TP and EB, but not DHTP, masculinized CA1 pyramidal cell field volume and neuronal soma size; CA3 was masculinized in both TP- and DHTP-treated females, while EB was ineffective. No effects were observed in cell density, number, or DG-GCL volume or due to adult hormone levels. Thus, prenatal androgens and estrogen influence sex differences in adult spatial navigation and exert differential effects on CA1 and CA3 pyramidal cell morphology. Hence, in addition to the previously reported postnatal component, there is also a prenatal component to the critical period in which gonadal steroids organize the neural mechanisms underlying sex differences in adult spatial ability.     

The effects of hippocampal and fimbria–fornix lesions on prepulse inhibition.

The present experiments tested the effects of conventional (dorsal aspiration and electrolytic) and excitotoxic (N-methyl-{d}-aspartate [NMDA]) hippocampal lesions and fimbria-fornix (FF) transection on prepulse inhibition (PPI) of startle response and on open-field activity. Activity was increased by FF transection and by conventional but not excitotoxic hippocampal lesions; complete NMDA lesion increased amphetamine-induced activity. Whereas dorsal hippocampal aspiration lesion disrupted PPI, the phenomenon was not affected by dorsal hippocampal. electrolytic lesion, partial or complete excitotoxic (NMDA) hippocampal lesions, or complete FF transection, which interrupted the cholinergic input to the hippocampus as well as the hippocampal-subicular input to the nucleus accumbens. Systemic apomorphine disrupted PPI in both FF-transected rats and their controls. It is suggested that the hippocampus is essential for PPI disruption rather than for PPI expression. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Sexual differentiation of play behavior in the ferret.

Three experiments examined the endocrine mechanisms responsible for sex differences in prepubertal play behavior of ferrets. In Exp I, 6 gonadally intact adolescent males exhibited higher levels of "stand-over" behavior than 6 females did in tests between 63 and 123 days of age with gonadally intact female partners of the same age. In Exp II, with 69 Ss, those Ss exposed to androgen or to ovarian steroids over Days 5–20 of postnatal life subsequently exhibited significantly higher levels of stand-over behavior in tests with females than did control females gonadectomized on Day 5 and not given steroids. None of the Ss in Exp II exhibited levels of stand-over behavior comparable to those of the gonadally intact males in Exp I. In Exp III, with 36 Ss, males gonadectomized and implanted subcutaneously with testosterone capsules on Day 70 and tested with females at 84–96 days of age exhibited levels of stand-over behavior comparable to those observed in Exp I in gonadally intact males of the same age (Weeks 12–24). Males gonadectomized on Day 70 and given no hormone at testing exhibited significantly lower levels of this behavior. Significantly lower levels were also exhibited by males gonadectomized on Day 35 and females gonadectomized on Day 70, regardless of whether they were tested with testosterone present after Day 70. Sex differences in the expression of prepubertal play behavior of ferrets apparently result from differential exposure of males and females to androgen over an extended postnatal period. (25 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Sex and social play in juvenile rats (Rattus norvegicus).

Four experiments were conducted to examine the effects of pretest social isolation, sex of the social stimulus, and test cage familiarity on sex differences in play fighting in 156 juvenile Long-Evans rats. Reliable sex differences were found only when Ss were tested after 6 days of isolation in undisturbed cages (Exp III). In contrast to weak sex effects, pretest isolation and test cage familiarity were robust variables influencing levels of play fighting in juveniles of both sexes. Results are discussed in reference to procedural differences among experimental approaches that have examined sex differences in social play. It is suggested that social investigatory behavior and play behavior appear to be reciprocally related. Hence, the sex difference in social play is accompanied by an apparent reversal in the sex effect seen with social investigation. (28 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Sex differences in glutamic acid decarboxylase mRNA in neonatal rat brain: implications for sexual differentiation

Sexual differentiation of rodent brain is dependent upon hormonal exposure during a "critical period" beginning in late gestation and ending in early neonatal life. Steroid hormone action at this time results in anatomical and physiological sexual dimorphisms in adult brain, but the mechanism mediating these changes is essentially unknown. The inhibitory neurotransmitter, GABA, is involved in regulation of sexually dimorphic patterns of behavior and gonadotropin secretion in the adult. Recent evidence suggests that during development GABA is excitatory and provides critical neurotrophic and neuromodulatory influences. We hypothesized that steroid-induced changes in GABAergic neurotransmission during this critical period are important mediators of sexual differentiation in brain. Therefore, we quantified levels of mRNA for GAD, the rate-limiting enzyme in GABA synthesis. On Postnatal Day 1, males had significantly higher levels of GAD mRNA in the dorsomedial nucleus, arcuate nucleus, and CA1 region of hippocampus. On Postnatal Day 15, after the critical period for sexual differentiation has ended, these differences were no longer present. We examined the role of gonadal steroids in regulating GAD by removing testes of males and administering testosterone to females at birth. Exposure to testosterone was correlated with increased GAD mRNA in the dorsomedial nucleus. A sex difference in GAD mRNA was also observed in the medial preoptic area, but the influence of testosterone was inconclusive. We conclude that sex differences in the GABAergic system during development are partially hormonally mediated, and that these differences may contribute to the development of sexually dimorphic characteristics in adult brain.     

Nerve growth factor attenuates cholinergic deficits following traumatic brain injury in rats

Traumatic brain injury (TBI) results in chronic derangements in central cholinergic neurotransmission that may contribute to posttraumatic memory deficits. Intraventricular cannula (IVC) nerve growth factor (NGF) infusion can reduce axotomy-induced spatial memory deficits and morphologic changes observed in medial septal cholinergic neurons immunostained for choline acetyltransferase (ChAT). We examined the efficacy of NGF to (1) ameliorate reduced posttraumatic spatial memory performance, (2) release of hippocampal acetylcholine (ACh), and (3) ChAT immunoreactivity in the rat medial septum. Rats (n = 36) were trained prior to TBI on the functional tasks and retested on Days 1-5 (motor) and on Day 7 (memory retention). Immediately following injury, an IVC and osmotic pump were implanted, and NGF or vehicle was infused for 7 days. While there were no differences in motor performance, the NGF-treated group had significantly better spatial memory retention (P < 0.05) than the vehicle-treated group. The IVC cannula was then removed on Day 7, and a microdialysis probe was placed into the dorsal hippocampus. After a 22-h equilibration period, samples were collected prior to and after administration of scopolamine (1 mg/kg), which evoked ACh release by blocking autoreceptors. The posttraumatic reduction in scopolamine-evoked ACh release was completely reversed with NGF. Injury produced a bilateral reduction in the number and cross-sectional area of ChAT immunopositive medial septal neurons that was reversed by NGF treatment. These data suggest that cognitive but not motor deficits following TBI are, in part, mediated by chronic deficits in cholinergic systems that can be modulated by neurotrophic factors such as NGF.     

Local inhibition of hippocampal nitric oxide synthase does not impair place learning in the Morris water escape task in rats

Recent studies have provided evidence that nitric oxide (NO) has a role in certain forms of memory formation. Spatial learning is one of the cognitive abilities that has been found to be impaired after systemic administration of an NO-synthase inhibitor. As the hippocampus has a pivotal role in spatial orientation, the present study examined the role of hippocampal NO in spatial learning and reversal learning in a Morris task in adult rats. It was found that N omega-nitro-L-arginine infusions into the dorsal hippocampus affected the manner in which the rats were searching the submerged platform during training, but did not affect the efficiency to find the spatial location of the escape platform. Hippocampal NO-synthase inhibition did not affect the learning of a new platform position in the same water tank (i.e. reversal learning). Moreover, no treatment effects were observed in the probe trials (i.e. after acquisition and after reversal learning), indicating that the rats treated with N omega-nitro-L-arginine had learned the spatial location of the platform. These findings were obtained under conditions where the NO synthesis in the dorsal hippocampus was completely inhibited. On the basis of the present data it was concluded that hippocampal NO is not critically involved in place learning in rats.     

Electrically evoked acetylcholine release from hippocampal slices is inhibited by the cannabinoid receptor agonist, WIN 55212-2, and is potentiated by the cannabinoid antagonist, SR 141716A

This study examined the effect of the cannabinoid receptor agonist, WIN 55212-2, on the electrically evoked release of [14C]acetylcholine (ACh) from superfused brain slices from the hippocampus, a region with a high density of cannabinoid receptors. A comparison was also made with [14C]ACh release from the nucleus accumbens, which has relatively fewer cannabinoid receptors. In the hippocampal slices, WIN 55212-2 produced a dose-dependent inhibition of [14C]ACh release, with an EC50 of 0.03 microM and a maximal inhibition of 81% at 1 microM. In the nucleus accumbens slices, WIN 55212-2 produced a weak inhibition of [14C]ACh release, which did not quite reach statistical significance. The inhibition of electrically evoked hippocampal [14C]ACh release by WIN 55212-2 could be prevented by the cannabinoid receptor antagonist, SR 141716A (EC50, 0.3-1.0 microM). In addition to antagonizing the effects of WIN 55212-2, SR 141716A alone produced a 2-fold potentiation of the electrically stimulated [14C]ACh release in this region (EC50, 0.1-0.3 microM). By contrast, in nucleus accumbens slices, no potentiation of the stimulated release of [14C]ACh release by SR 141716A was observed. Basal [14C]ACh release was unaffected by WIN 55212-2 or SR 141716A in either area. These results suggest that cannabinoid receptor activation can produce a strong inhibition of ACh release in the hippocampus. Furthermore, the potentiation of ACh release in the hippocampus by SR 141716A alone suggests either that this compound is an inverse agonist at cannabinoid receptors or it is antagonizing the actions of an endogenous ligand acting on these receptors.     

Effects of CDP-choline treatment on neurobehavioral deficits after TBI and on hippocampal and neocortical acetylcholine release

The exogenous administration of cytidine-5'-diphosphate (CDP)-choline has been used extensively as a brain activator in different neurological disorders that are associated with memory deficits. A total of 50 rats were utilized to (a) determine whether exogenously administered CDP-choline could attenuate posttraumatic motor and spatial memory performance deficits and (b) determine whether intraperitoneal (i.p.) administration of CDP-choline increases acetylcholine (ACh) release in the dorsal hippocampus and neocortex. In the behavioral study, traumatic brain injury (TBI) was produced by lateral controlled cortical impact (2-mm deformation/6 m/sec) and administered CDP-choline (100 mg/kg) or saline daily for 18 days beginning 1 day postinjury. At 1 day postinjury, rats treated with CDP-choline 15 min prior to assessment performed significantly better than saline-treated rats. Between 14-18 days postinjury, CDP-choline-treated rats had significantly less cognitive (Morris water maze performance) deficits that injured saline-treated rats. CDP-choline treatment also attenuated the TBI-induced increased sensitivity to the memory-disrupting effects of scopolamine, a muscarinic antagonist. The microdialysis studies demonstrated for the first time that a single i.p. administration of CDP-choline can significantly increase extracellular levels of ACh in dorsal hippocampus and neocortex in normal, awake, freely moving rats. This article provides additional evidence that spatial memory performance deficits are, at least partially, associated with deficits in central cholinergic neurotransmission and that treatments that enhance ACh release in the chronic phase after TBI may attenuate cholinergic-dependent neurobehavioral deficits.     

Quantitation of age-related mitochondrial DNA deletions in rat tissues shows that their pattern of accumulation differs from that of humans

We studied the postnatal development of the release of acetylcholine (ACh) and of presynaptic, release-inhibiting muscarinic autoreceptors in the rat hippocampus. To this end, hippocampal slices (350 microns thick) from rats of various postnatal ages (postnatal day 3 [P3] to P16) were preincubated with [3H]choline and stimulated twice (S1, S2: 360 pulses, 2 ms, 3 Hz, 60 mA) during superfusion with physiological buffer containing hemicholinium-3 (10 microM). In parallel, the activities of hemicholinium-sensitive high-affinity choline uptake (HACU, in synaptosomes) and of choline acetyltransferase (ChAT, in crude homogenates) were determined as markers for the cholinergic ingrowth. In hippocampal slices preincubated with [3H]choline, the electrically evoked overflow of 3H at S1 increased from 0.11 (P3) to 0.81% of tissue 3H (P16), the latter value being still much lower than that of hippocampal slices from adult rats (2.89% of tissue 3H). Already at P3 the evoked overflow of 3H was Ca(2+)-dependent and sensitive to tetrodotoxin, indicating an action potential-evoked exocytotic mechanism of ACh release. The muscarinic agonist oxotremorine (1 microM) significantly inhibited the evoked ACh release in hippocampal slices with increasing effectivity from P4 to P16; no significant effect was detectable at P3. The ACh esterase inhibitor physostigmine and the muscarinic antagonist atropine (1 microM, each) exhibited significant inhibitory and facilitatory effects, respectively, only at P15-16. The specific activities of both hippocampal HACU (pmoles/mg protein/min) and ChAT (nmoles/mg protein/min) continuously increased from P3 to P16. It is concluded (1) that cholinergic nerve terminals arriving at the hippocampal formation during postnatal ingrowth are already endowed with the apparatus for action potential-induced, Ca(2+)-sensitive (exocytotic) ACh release; (2) that, in contrast, the expression of presynaptic muscarinic autoreceptors on these cholinergic axon terminals is delayed; and (3) that autoinhibition due to endogenous ACh develops even later, probably when the density of presynaptic terminals in the hippocampus and hence, the concentration of released ACh has reached a suprathreshold value.     

Disruption of spatial but not object-recognition memory by neurotoxic lesions of the dorsal hippocampus in rats.

Ischemia-induced cell loss in the CA1 region of the dorsal hippocampus results in severe deficits on delayed non-matching-to-sample (DNMS), whereas hippocampectomy produces little or no impairment, suggesting that partial hippocampal damage is more detrimental to DNMS performance than total ablation. To test this hypothesis, rats with or without preoperative DNMS training were given partial cytotoxic lesions of the dorsal hippocampus. When tested, neither group displayed any DNMS deficits despite widespread cell loss in the CA1 and other regions of the dorsal hippocampus. In the final experiments, rats tested previously on DNMS were found to be impaired on the Morris water maze. The finding that partial hippocampal lesions disrupt spatial memory while leaving object-recognition memory intact indicates a specialized role for the hippocampus in mnemonic processes. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Perplexing effects of hippocampal lesions on latent inhibition: a neural network solution

Experimental data indicate that hippocampal lesions might impair, spare, or even facilitate latent inhibition (LI). Furthermore, when LI is impaired by the lesions, it might be reinstated by haloperidol administration. The present article applies a neural network model of classical conditioning (N. A. Schmajuk, Y. W. Lam, & J. A. Gray, 1996) to investigate the possible causes of these puzzling results. According to the model, LI is manifested because preexposure of the conditioned stimulus (CS) reduces Novelty, defined as proportional to the sum of the mismatches between predicted and observed events, thereby reducing attention to the CS and retarding conditioning. It is assumed that hippocampal lesions affect the prediction of events. Computer simulations reveal that, depending on the behavioral protocol (i.e., procedure and total time of CS preexposure), Novelty in hippocampal lesioned animals might be larger, equal, or smaller (corresponding to smaller, equal, or larger LI) than in normal controls. Reinstatement of LI by haloperidol administration is explained by assuming that dopaminergic antagonists decrease the value of Novelty, when Novelty increases following hippocampal lesions.     

Spatial learning impairment parallels the magnitude of dorsal hippocampal lesions, but is hardly present following ventral lesions

The hippocampus plays an essential role in spatial learning. To investigate whether the whole structure is equally important, we compared the effects of variously sized and localized hippocampal aspiration lesions on spatial learning in a Morris water maze. The volume of all hippocampal lesions was determined. Dorsal hippocampal lesions consistently impaired spatial learning more than equally large ventral lesions. The dorsal lesions had to be larger than 20% of the total hippocampal volume to prolong final escape latencies. The acquisition rate and precision on a probe test without platform were sensitive to even smaller dorsal lesions. The degree of impairment correlated with the lesion volume. In contrast, the lesions of the ventral half of the hippocampus spared both the rate and the precision of learning unless nearly all of the ventral half was removed. There was no significant effect of the location (dorsal or ventral) of damage to the overlying neocortex only. In conclusion, the dorsal half of the hippocampus appears more important for spatial learning than the ventral half. The spatial learning ability seems related to the amount of damaged dorsal hippocampal tissue, with a threshold at about 20% of the total hippocampal volume, under which normal learning can occur.     

Temperament in the Rat: Sex Differences and Hormonal Influences on Harm Avoidance and Novelty Seeking.

This study showed large and consistent individual differences in 64 rats (32 males) in the hole board and canopy test, which are considered to measure exploration and anxiety, respectively. Nonestrous females were more active than males and nose poked more in the hole board. In the canopy test, nonestrous females, compared with males, showed greater intraindividual variability in time spent outside the protective canopy. Estrous females spent significantly more time outside the canopy. Gonadectomy reduced nose poking in males and hole board locomotion in both sexes. Principal-components analysis disclosed 2 temperamental dimensions reflecting harm avoidance and novelty seeking. More males had high levels of psychometric harm avoidance, and fewer males than females had a low-harm-avoidance/high-novelty-seeking, sanguine profile. (PsycINFO Database Record (c) 2010 APA, all rights reserved)