Differential behavioral effects following microinjection of an NMDA antagonist into nucleus accumbens subregions.

Recent studies have demonstrated the existence of two distinct regions within the nucleus accumbens (N.Acc) known as "core" and "shell". In order to investigate whether the behavioral functions of excitatory amino acid receptors differed between these two subregions, rats were administered microinjections of 2-amino-5-phosphonovaleric acid (AP-5), a competitive NMDA antagonist (0, 0.05, 0.2, 0.5, 1.0 microgram/0.5 microliter) into selected central and medial regions of the accumbens. The central and medial sites were assumed to correspond approximately to core and shell subregions, respectively. The animals were tested in two exploratory tasks: the open field and a novel object test. In the open field test, AP-5 significantly decreased peripheral locomotion and center rearing frequency in the central but not the medial group. Locomotion and rearing were not affected by AP5 infusion into a control site, the anterior dorsal striatum (ADS). In the novel object test, animals were tested in the same open field, with prior habituation, and with several novel objects placed within it. In this test, infusions of AP-5 (0, 1.0 microgram/0.5 microliter) decreased the number and duration of contacts with the novel objects in the central but not the medial group. In addition, peripheral and center locomotion were decreased by AP-5 infusions into the central site, whether objects were present or not. In contrast, AP-5 infusions into the medial site elicited an increase in peripheral locomotion in both stimulus conditions. These findings provide behavioral-pharmacological evidence that the central and medial subregions of the nucleus accumbens can be differentiated.(ABSTRACT TRUNCATED AT 250 WORDS)

Excitotoxic lesions of the core and shell subregions of the nucleus accumbens differentially disrupt body weight regulation and motor activity in rat.

The behavioral effects of bilateral N-methyl-D-aspartate (NMDA) lesions of the core and medial shell subregions of the nucleus accumbens were evaluated in rats. Body weight was monitored for 2 weeks following surgery. Locomotor activity and open field behavior were recorded 1 week after surgery. The core-lesion group had difficulty recovering from the lesion and had significantly lower weights throughout the experiment. The shell-lesion group had normal recovery and weighed significantly more than controls over the course of the experiment. In the activity cage test, the core-lesion group was hyperactive when compared to controls and to the shell-lesion group. Activity of the shell-lesion group was similar to that of their sham-controls. Three weeks postlesion, the core-lesion group was still significantly more active. In the open field test, peripheral locomotion scores were significantly higher in the core-lesion group when compared to their controls, whereas the scores of the shell-lesion group were similar to controls. In the other open field measures, both lesion groups were hyperactive; however, the scores of core-lesion group were significantly higher than those of the shell-lesion group on all measures. Histological analysis indicated small, discrete areas of damage within the core or medial shell accumbens regions. These preliminary results suggest that these two subregions can be behaviorally differentiated.

Excitatory amino acid receptors within nucleus accumbens subregions differentially mediate spatial learning in the rat.

The present experiments investigated the effects of excitatory amino acid antagonists, infused into core and shell subregions of the nucleus accumbens, on spatial behavior in the rat. A food-search task was used, in which animals learn a specific pattern of food gathering; duration of each trial (time taken to gather all four pellets) and number of errors (visits to empty holes) were measured. In experiment 1, animals first underwent training, and subsequently were given microinfusions of either D-2-amino-5 phosphonopentanoic acid (AP-5), an N-methyl-d-aspartate (NMDA) antagonist (0, 0.2, 1.0µg/0.5µl), or 6,7-dinitroquinoxaline-2,3-dione (DNQX), an antagonist of alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) and kainate receptors (0, 0.075, 0.75µg/0.5µl). AP-5-significantly increased trial duration in both core and shell groups, but increased errors only in the core group. DNQX treatment also impaired performance in both groups, but the effect was greater in the core group compared with the shell group. In experiment 2, animals were treated during acquisition. Rats infused with AP-5 (1µg/0.5µl) took significantly longer to finish trials, made more errors and showed a marked learning impairment across days. AP-5 impaired learning in both core and shell groups, but the disruption was significantly greater in the core group. DNQX (0.75µg/0.5µl) also impaired learning when infused into the core during acquisition; however, the pattern of disruption contrasted markedly with that of AP-5. DNQX in the shell had no effect on trial duration during learning. It is hypothesized that both NMDA and non-NMDA receptors in the nucleus accumbens mediate spatial learning and performance, and that NMDA receptors may have a relatively more important role in memory or retrieval mechanisms. Moreover, the core subregion may be preferentially involved in the control of spatial behavior.

Prenatal protein malnutrition and home orientation in the rat.

Home orienting behavior was studied during the first 11 days of life in prenatally protein-malnourished and well-nourished rat pups, both groups having been reared by well-nourished mothers since birth. On all days of testing, mean weights were compromised in the prenatally malnourished pups relative to their well-nourished age controls (body weight deficit = 19-29%). Eye opening was also significantly delayed in the malnourished group. On the test of homing behavior, malnourished pups were significantly impaired in their ability to locate the nest on days 9 and 11. The effect was not related to activity levels of the pups, which were generally similar in the two nutritional groups. Thus, prenatal malnutrition disturbs the development of the homing response in the early postnatal period.

Substance dependence as a compulsive behavior.

A compulsion to take a drug combined with a loss of control in limiting intake is the defining feature of substance dependence or addiction, and is the conceptual framework for the criteria of substance dependence or addiction outlined by the World Health Organization and the American Psychiatric Association. However, defining exactly what constitutes loss of control and compulsive drug taking at the level of animal models is a daunting task, and it is clear that no validated animal model exists for the whole syndrome of addiction. The present discussion redefines loss of control as a narrowing of the behavioral repertoire toward drug-seeking behavior and suggests that there are many sources of reinforcement that contribute to this behavioral focus on drug seeking. Evidence is presented demonstrating separate animal models for many of these sources of reinforcement as well as for most of the criteria for substance dependence. Evidence is also presented showing that the brain neurochemical systems involved in processing drug reward are altered by chronic drug exposure to contribute additional sources of reinforcement. Challenges for the future involve not only elucidation of the neurobiological substrates of the different behavioral components of addiction, but better animal models of these components with which to effect such studies.

Effects of cocaine and GBR-12909 on brain stimulation reward.

Cocaine and GBR-12909, two dopamine reuptake blockers, were administered in a multiple current rate-frequency curve-shift test of intracranial self-stimulation (ICSS) reward in rats with medial forebrain bundle (MFB) electrodes. Acute injections of cocaine (0, 5, 15, 30 mg/kg, IP) increased ICSS reward at all currents (501, 316, 200 microAmps) as measured by decrease half-maximal frequency threshold. Cocaine also increased operant motor performance but only at the low current. In addition, cocaine increased dynamic interval at the highest dose at all currents. Similar treatment with GBR-12909 (0, 5, 10, 20 mg/kg, IP) significantly increased ICSS reward (decreased threshold) especially at the medium dose in all currents and had no significant effects on operant motor performance or dynamic interval. The major novel finding of the present study is that the rewarding effects of both drugs was not dependent on the choice of stimulation current, which is discussed as simplifying future psychophysical testing of psychostimulant drugs in the ICSS rate-frequency curve-shift paradigm.

The Healthy Neighborhoods Project: a local health department's role in catalyzing community development.

Studies show that community development approaches to health education may lead not only to improved social, economic, and health status but also to increased individual participation in health education and preventive health care activities. However, because of categorical funding restraints and philosophical issues, local health departments have rarely given control of defining project outcomes to the community. One such project was in a low-income urban neighborhood in the San Francisco Bay Area. In this Healthy Neighborhoods Project, the health department catalyzed community development and organization in a multiethnic public housing complex. As a result, an empowered community successfully advocated to improve public safety by installing street speed humps and increased street lighting. After project completion, residents initiated several additional health actions, including the removal of a neighborhood tobacco billboard. This article describes the project, which may serve as a model for other urban public health programs to explore their role in community empowerment.

Seniors-on-line: introducing older people to technology.

Retired Engineers are playing an important role in ensuring that older people are not excluded from the benefits of technological advances. Technology is playing an increasingly important role in the lives of older people as it is incorporated into assistive devices, home security, access to health care, banking, communication and many other areas. However, if older people are unfamiliar with new technologies and find them daunting, they may not benefit fully from these advances. In order to minimize difficulties arising from unfamiliarity with technology, an introductory computer course was offered to people aged 55 and over. Teaching methods appropriate to the needs of older people were used: small classes, students and instructors from same age cohort, slow pace of presentation and ample opportunity to ask questions. Retired Engineers make up the majority of instructors. Three hundred and sixty nine older people have participated in the course and most plan to continue using a computer.

Bringing it home: Australian social workers implement leadership program values.

Two senior social workers from major teaching hospitals in Adelaide, South Australia, were the first participants from Australia in Mount Sinai's leadership exchange program, from November 1, 1990 to January 31, 1992. The two participants were eager, excited, and strongly committed to participating fully in the project. They left Australia with the intent to bring back new skills, insights, and vision--for themselves, their hospitals, and the social work profession. They returned with advanced skills and insights and remarkably altered attitudes toward research, writing for publication, their relationship with academia, leadership and management, the development of innovative programs, and information systems. And, they returned with a clear international perspective of their profession, its uniqueness and its opportunities.

Social work leadership development through international exchange.

Social workers in large bureaucratic settings face the pressure to define their service in relation to other professional disciplines and to maintain a quality service despite conflicting mandates and economic restraints. Few strategies exist for providing training and education to senior social workers in order to help them develop leadership roles in multidisciplinary environments. This paper examines the characteristics and qualities necessary to provide social work leadership in a complex hospital environment. The ideas emerged from an international leadership exchange program with The Mount Sinai Medical Center in New York City. Aspects of this experience are used to illustrate leadership roles.

Glutamate receptors in the nucleus accumbens shell control feeding behavior via the lateral hypothalamus.

The nucleus accumbens in a brain region considered to be important in the regulation of appetitive behavior and reinforcement. The accumbens receives afferent input from corticolimbic and thalamic structures, which is primarily coded by excitatory amino acids (EAAs). The present studies investigated the role of EAA input to the nucleus accumbens in feeding behavior in rats, in two recently characterized subregions of the accumbens, the "core" and "shell". In the first series of experiments, it was shown that blockade of alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) and kainate glutamate receptors in the medial part of the accumbens, corresponding to the medial shell subregion, resulted in a pronounced feeding response. Bilateral microinfusion of 6,7-dinitroquinoxaline-2,3-dione (DNQX, 0.25-0.75 micrograms/0.5 microliters), 6-cyano-7-nitroquinoxaline (CNQX, 0.75-1.5 micrograms), and 2,3-dihydroxy-6-nitro-7-sulfamoylbenzo-(F) quinoxaline (NBQX, 0.2-1.0 micrograms) markedly stimulated food intake immediately following infusion, in a dose-dependent manner. Infusion of DNQX into the central accumbens region, corresponding to the core, did not elicit feeding. Infusion of the NMDA antagonists 2-amino-5-phosphonopentanoic acid (AP-5) and MK-801 (dizocilpine maleate) did not elicit feeding in either region. The feeding response to DNQX was blocked by local coinfusion of AMPA. Systemic pretreatment with naltrexone (5 mg/kg) had no effect on the DNQX-feeding response; however, prior systemic administration of both D-1 and D-2 antagonists reduced the response by half, suggesting a modulatory role for dopamine in the response. Moreover, the feeding response was completely inhibited by concurrent infusion of the GABAA agonist muscimol (10, 25 ng) into the lateral hypothalamus, a major projection area of the accumbens shell. These findings demonstrate a selective role for non-NMDA receptors in the nucleus accumbens shell in ingestive behavior, and suggest an important functional link between two major brain regions involved in reward, the nucleus accumbens and lateral hypothalamus.