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PubMed2001

The testosterone metabolite and neurosteroid 3alpha-androstanediol may mediate the effects of testosterone on conditioned place preference.

The abuse of androgens may be related to their ability to produce positive, hedonic interoceptive effects. Conditioned Place Preference (CPP) has been used in many experiments to examine hedonic effects of drugs. This review is focused on studies from our laboratory that utilized CPP to examine potential positive hedonic effects of testosterone (T), and its androgenic metabolite dihydrotestosterone (DHT), and its metabolite 3alpha-androstanediol (3alpha-diol). We hypothesized that administration of a high concentration of 3alpha-diol would produce a CPP, pharmacological concentrations of plasma androgens, and alter androgen receptors (AR) and the function of GABA(A)/benzodiazepine receptor complexes (GBR). In our studies, we observed that systemic 3alpha-diol (1.0 mg/kg) prior to exposure to the non-preferred side of a CPP chamber significantly increased preference for the non-preferred side of the chamber compared to baseline preference and homecage controls. Furthermore, administration of T, DHT, or 3alpha-diol increased levels of these androgens, decreased ARs (decreased seminal vesicle weight and intrahypothalamic AR) and GBR function (decreased GABA-stimulated chloride influx in cortical synaptoneurosomes, and muscimol binding in the hippocampus compared to control groups). With systemic administration of 3alpha-diol that enhanced CPP, concentrations of 3alpha-diol were increased in the nucleus accumbens (NA). Central implants of T, DHT, or 3alpha-diol to the NA also produced a CPP compared to baseline preference and vehicle controls. These data indicate that systemic 3alpha-diol is more effective at enhancing CPP and increasing circulating 3alpha-diol levels than is T or DHT and that central administration of 3alpha-diol to the NA can condition a place preference. These findings indicate that 3alpha-diol produces positive hedonic effects and suggest that T's variable effects on CPP may be due in part to T's metabolism to 3alpha-diol.

Androstane-3,17-diol↗
PubMed2004

Positive geotaxis in infant rats (Rattus norvegicus): a natural behavior and a historical correction.

Infant rats (Rattus norvegicus) placed on a shallow incline (2 degrees, 4 degrees, or 8 degrees) oriented and moved downhill within 1 min; that is, they displayed positive geotaxis. Their downhill translocation increased with angle of inclination. A variety of possible behavioral elements (e.g., initial orientation, rotational movements, ambulatory velocities) were eliminated as explanations of the geotaxis. Wall contact was recognized as a determinative event: Pups on the inclines showed no orientation with respect to the geogravitational stimulus before contacting a wall. The event of wall contact, however, evoked reliable downhill orientation and more linear movements. Positive geotaxis was created by pups' orientation against walls and an associated increase in movement velocity. This is a distinct perspective on a behavioral response that replaces a traditionally misinterpreted phenomenon. The authors discuss the ecological validity and historical context of these findings.

Animals↗
PubMed1999

Visual homing in analog hardware.

Insects of several species rely on visual landmarks for returning to important locations in their environment. The "average landmark vector model" is a parsimonious model which reproduces some aspects of the visual homing behavior of bees and ants. To gain insights in the structure and complexity of the neural apparatus that might underly the navigational capabilities of these animals, the average landmark vector model was implemented in analog hardware and used to control a mobile robot. The experiments demonstrate that the apparently complex task of visual homing might be realized by simple and mostly peripheral neural circuits in insect brains.

Animals↗
PubMed2000

Activity in human frontal cortex associated with spatial working memory and saccadic behavior.

We examined, with event-related fMRI, two hypotheses about the organization of human working memory function in frontal cortex: (1) that a region immediately anterior to the frontal eye fields (FEF) (superior frontal cortex, SFC) is specialized for spatial working memory (Courtney, et al., 1998); and (2) that dorsolateral prefrontal cortex (PFC) plays a privileged role in the manipulation of spatial stimuli held in working memory (Owen, et al., 1996; Petrides 1994). Our delayed-response task featured 2-D arrays of irregularly arranged squares that were highlighted serially in a random sequence. The Forward Memory condition required maintenance of the spatio-temporal sequence, the Manipulate Memory condition required reordering this sequence into a new spatially defined order, the Guided Saccade condition required saccades to highlighted squares in the array, but no memory, and the Free Saccade condition required self-paced, horizontal saccades. The comparison of fMRI signal intensity associated with 2-D saccade generation (Guided Saccades) versus fMRI signal intensity associated with the delay period of the working memorials condition revealed no evidence for greater working memory-related activity than saccade-related activity in SFC in any individual subject, nor at the level of the group, and greater 2-D saccade than delay-period activity in three of five subjects. These results fail to support the hypothesis that spatial working memory-related activity is represented preferentially in a region of SFC anterior to the FEF (Courtney, et al., 1998). The comparison of maintenance versus manipulation of spatio-temporal information in working memory revealed significantly greater activity associated with the latter in dorsolateral PFC, but not in ventrolateral PFC or in SFC. These results suggest that the delay-related function of SFC is limited to the maintenance of spatial information, and that this region does not support the nonmnemonic executive control functions supported by dorsolateral PFC. These results also indicate that the preferential recruitment of dorsolateral PFC for the manipulation of information held in working memory applies to tasks employing spatial stimuli, as well as to tasks employing verbal stimuli (D'Esposito, et al., 1999); Petrides et al., 1993; Postle et al., 1999).

Acoustic Stimulation↗
PubMed2001

Compulsive checking behavior of quinpirole-sensitized rats as an animal model of Obsessive-Compulsive Disorder(OCD): form and control.

BACKGROUND: A previous report showed that the open field behavior of rats sensitized to the dopamine agonist quinpirole satisfies 5 performance criteria for compulsive checking behavior. In an effort to extend the parallel between the drug-induced phenomenon and human obsessive-compulsive disorder (OCD), the present study investigated whether the checking behavior of quinpirole rats is subject to interruption, which is an attribute characteristic of OCD compulsions. For this purpose, the rat's home-cage was placed into the open field at the beginning or the middle of a 2-hr test. RESULTS: Introduction of the home-cage reduced checking behavior, as rats stayed inside the cage. After 40 min, checking resurfaced, as quinpirole rats exited the home-cage often. An unfamiliar cage had no such effects on quinpirole rats or saline controls. CONCLUSIONS: Checking behavior induced by quinpirole is not irrepressible but can be suspended. Results strengthen the quinpirole preparation as an animal model of OCD compulsive checking.

Animals↗
PubMed1977

Interpersonal distance behavior of mentally retarded and nonretarded children.

The investigators compared interpersonal-distance choice behavior of 60 mildly retarded children and 60 nonretarded children of comparable MAs to a male adult stranger. Contrary to the original prediction, stemming from Zigler's negative-reaction tendency formulation, interpersonal distance by retarded children was not generally different from that of nonretarded children. However, analysis of the interaction between IQ group and approach condition (child approaching adult or adult approaching child) indicated that retarded children preferred greater distance from the approaching adult than did nonretarded children. This result raises the possibility that perception of lessened personal control by retarded children stimulated a stronger avoidance reaction.

Adolescent↗
PubMed1998

Unilateral hippocampal lesions in newborn and adult rats: effects on spatial memory and BDNF gene expression.

Subcortical damage at birth often produces more severe deficits than similar lesions in an adult. In the present study, effects of unilateral electrolytic hippocampal ablations made on postnatal day 1 or in 3-month-old adult rats, were compared. Exploratory behavior and spatial navigation in the Morris water maze (MWM) were assessed 8 and 20 weeks after hippocampal damage. Rats with neonatal damage did not respond to novelty in the environment and did not learn to find the hidden platform in the MWM. Rats lesioned as adults did learn the water maze task, but slower than controls. We hypothesized that behavioral deficits observed in rats lesioned at birth, may be due, in part, to neurochemical dysfunction of the contralateral hippocampus. Specifically, cholinergic and GABAergic neurotransmission were assessed by measuring choline-acetyltransferase (ChAT) and GABAdecarboxylase (GAD) activity. In addition, nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF) mRNA levels were assayed in the remaining (contralateral) hippocampus. Of these molecules, only BDNF gene expression was significantly reduced (by 30%) at 8 and 20 weeks after neonatal and adult unilateral ablation. The similar reduction in BDNF mRNA in both treatment groups does not correspond with the lesion's differential effect on memory function. However, the more severe learning impairment after neonatal lesion may reflect increased dependence on trophins during development.

Aging↗
PubMed1988

A model of spatial localization and its application to strabismus.

Visually guided, spatially oriented behavior involves an ongoing integration of signals regarding the loci of the retinal images and the position and orientation of the eye. In the strabismic this requires an altered spatial metric resulting from a functional readaptation to avoid confusion and diplopia. A comparator mechanism for evaluating these two signals is presented. A case report using "disruptive" therapeutic procedures that deliberately alter the strabismic's visual-postural control system is presented. A treatment plan for altering the anomalous binocular link, a characteristic of the well adapted strabismic, is described and related to the comparator mechanism.

Adaptation, Physiological↗
PubMedDate not supplied

[Spatial-motor asymmetry in rat behavior].

The experiments were carried out on rats in three different mazes: U-shape, complicated linear and 12-beam radial. Series of tests differed by succession of rats learning in the mazes and the character of reinforcement. Most of the rats manifested a spatial-motor asymmetry (SMA) in all used situations. Under all conditions SMA increased in the process of learning parallel to a decrease of the errors number or the time of the task performing. In the group of rats sequently learning in different mazes, the direction of moving changed with changes in spatial characteristics of the medium. Preliminary training of rats in conditions creating SMA, promoted its acceleration in new conditions. The conclusion is made that the rats have no physiological mechanism which rigidly fixes a single (in all conditions) direction of runs. SMA is considered as a behavioural tactics which is corrected in the process of training and which provides for an adequate behaviour.

Animals↗
PubMed1998

The gradient of spatial auditory attention in free field: an event-related potential study.

Young adult subjects attended selectively to brief noise bursts delivered in free field via a horizontal array of seven loudspeakers spaced apart by 9 degrees of angle. Frequent "standard" stimuli (90%) and infrequent "target/deviant" stimuli (10%) of increased bandwidth were delivered at a fast rate in a random sequence equiprobably from each speaker. In separate runs, the subjects' task was to selectively attend to the leftmost, center, or rightmost speaker and to press a button to the infrequent "target" stimuli occurring at the designated spatial location. Behavioral detection rates and concurrently recorded event-related potentials (ERPs) indicated that auditory attention was deployed as a finely tuned gradient around the attended sound source, thus providing support for gradient models of auditory spatial attention. Furthermore, the ERP data suggested that the spatial focusing of attention was achieved in two distinct stages, with an early more broadly tuned filtering of inputs occurring over the first 80-200 msec after stimulus onset, followed by a more narrowly focused selection of attended-location deviants that began at around 250 msec and closely resembled the behavioral gradient of target detections.

Acoustic Stimulation↗
PubMed1995

L-nitroarginine reduces hippocampal mediation of place learning in the rat.

Based on previous results it was hypothesized that the neural substrate of the acquisition of place learning during inhibition of the nitric oxide synthesizing enzyme (NOS) by L-nitroarginine (L-N-ARG) differs from the neural substrate of normal task acquisition by a reduced or abolished participation of the hippocampus. This hypothesis was tested in two independent experiments. In Experiment 1 the behavioral consequences of bilateral transection of the fimbria-fornix--a lesion that abolishes normal hippocampal function--were investigated in animals that had acquired the task after either a vehicle control pretreatment or a 5-day pretreatment period during which near-total inhibition of NOS had been accomplished by L-N-ARG injections. While fimbria-fornix transections significantly impaired task performance in normal animals the rats which had acquired the task during NOS inhibition did not reveal a lesion-associated impairment. In Experiment 2 four groups of rats were studied: two groups initially received bilateral transection of the fimbria-fornix, while the two others were subjected to sham surgery. Subsequently, one of the fimbria-fornix-transected and one of the sham-operated groups received a 10-day period of L-N-ARG injections, while the two remaining groups received saline control injections. During the final 5 days of injections the four groups were subjected to training on the place-learning task. While NOS inhibition clearly impaired task acquisition in the sham-operated animals, L-N-ARG administration in fimbria-fornix-transected animals failed to impair place-learning acquisition.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗