Cocaine-predictive stimulus induces drug-seeking behavior and neural activation in limbic brain regions after multiple months of abstinence: Reversal by D1 antagonists

The conditioning of cocaine's subjective actions with environmental stimuli may be a critical factor in long-lasting relapse risk associated with cocaine addiction. To study the significance of learning factors in persistent addictive behavior as well as the neurobiological basis of this phenomenon, rats were trained to associate discriminative stimuli (SD) with the availability of i.v. cocaine vs. nonrewarding saline solution, and then placed on extinction conditions during which the i.v. solutions and SDs were withheld. The effects of reexposure to the SD on the recovery of responding at the previously cocaine-paired lever and on Fos protein expression then were determined in two groups. One group was tested immediately after extinction, whereas rats in the second group were confined to their home cages for an additional 4 months before testing. In both groups, the cocaine SD, but not the non-reward SD, elicited strong recovery of responding and increased Fos immunoreactivity in the basolateral amygdala and medial prefrontal cortex (areas Cg1/Cg3). The response reinstatement and Fos expression induced by the cocaine SD were both reversed by selective dopamine D1 receptor antagonists. The undiminished efficacy of the cocaine SD to elicit drug-seeking behavior after 4 months of abstinence parallels the long-lasting nature of conditioned cue reactivity and cue-induced cocaine craving in humans, and confirms a significant role of learning factors in the long-lasting addictive potential of cocaine. Moreover, the results implicate D1-dependent neural mechanisms within the medial prefrontal cortex and basolateral amygdala as substrates for cocaine-seeking behavior elicited by cocaine-predictive environmental stimuli.

Providing health information to the general public: a survey of current practices in academic health sciences libraries*

A questionnaire was mailed to 148 publicly and privately supported academic health sciences libraries affiliated with Association of American Medical Colleges (AAMC)–accredited medical schools in the United States and Canada to determine level of access and services provided to the general public. For purposes of this study, “general public” was defined as nonaffiliated students or health care professionals, attorneys and other nonhealth-related professionals, patients from affiliated or other hospitals or clinics, and general consumers. One hundred five (71%) libraries responded. Results showed 98% of publicly supported libraries and 88% of privately supported libraries provided access to some or all of the general public. Publicly supported libraries saw greater numbers of public patrons, often provided more services, and were more likely to circulate materials from their collections than were privately supported libraries. A significant number of academic health sciences libraries housed a collection of consumer-oriented materials and many provided some level of document delivery service, usually for a fee. Most allowed the public to use some or all library computers. Results of this study indicated that academic health sciences libraries played a significant role in serving the information-seeking public and suggested a need to develop written policies or guidelines covering the services that will be provided to minimize the impact of this service on primary clientele.

Information needs of rural health professionals: a review of the literature

This review analyzes the existing research on the information needs of rural health professionals and relates it to the broader information-needs literature to establish whether the information needs of rural health professionals differ from those of other health professionals. The analysis of these studies indicates that rural health practitioners appear to have the same basic needs for patient-care information as their urban counterparts, and that both groups rely on colleagues and personal libraries as their main sources of information. Rural practitioners, however, tend to make less use of journals and online databases and ask fewer clinical questions; a difference that correlates with geographic and demographic factors. Rural practitioners experience pronounced barriers to information access including lack of time, isolation, inadequate library access, lack of equipment, lack of skills, costs, and inadequate Internet infrastructure. Outreach efforts to this group of underserved health professionals must be sustained to achieve equity in information access and to change information-seeking behaviors.

Outreach to public health professionals: lessons learned from a collaborative Iowa public health project*

In 1995, the National Library of Medicine (NLM) and the Public Health Service (PHS) recommended that special attention be given to the information needs of unaffiliated public health professionals. In response, the National Network of Libraries of Medicine (NN/LM) Greater Midwest Region initiated a collaborative outreach program for public health professionals working in rural east and central Iowa. Five public health agencies were provided equipment, training, and support for accessing the Internet. Key factors in the success of this project were: (1) the role of collaborating agencies in the implementation and ongoing success of information access outreach projects; (2) knowledge of the socio-cultural factors that influence the information-seeking habits of project participants (public health professionals); and (3) management of changing or varying technological infrastructures. Working with their funding, personnel from federal, state, and local governments enhanced the information-seeking skills of public health professionals in rural eastern and central Iowa communities.

Relationship between psychostimulant-induced "high" and dopamine transporter occupancy.

The ability of cocaine to inhibit the dopamine transporter (DAT) appears to be crucial for its reinforcing properties. The potential use of drugs that produce long-lasting inhibition of the DAT as a mean of preventing the "high" and reducing drug-seeking behavior has become a major strategy in medication development. However, neither the relation between the high and DAT inhibition nor the ability to block the high by prior DAT blockade have ever been demonstrated. To evaluate if DAT could prevent the high induced by methylphenidate (MP), a drug which like cocaine inhibits the DAT, we compared the responses in eight non-drug-abusing subjects between the first and the second of two MP doses (0.375 mg/kg, i.v.) given 60 min apart. At 60 min the high from MP has returned to baseline, but 75-80% of the drug remains in brain. Positron-emission tomography and [11C]d-threo-MP were used to estimate DAT occupancies at different times after MP. DAT inhibition by MP did not block or attenuate the high from a second dose of MP given 60 min later, despite a 80% residual transporter occupancy from the first dose. Furthermore some subjects did not perceive a high after single or repeated administration despite significant DAT blockade. These results indicate that DAT occupancy is not sufficient to account for the high, and that for DAT inhibitors to be therapeutically effective, occupancies > 80% may be required.

A sensory brain map for each behavior?

Multiple brain maps are commonly found in virtually every vertebrate sensory system. Although their functional significance is generally relatively little understood, they seem to specialize in processing distinct sensory parameters. Nevertheless, to yield the stimulus features that ultimately elicit the adaptive behavior, it appears that information streams have to be combined across maps. Results from current lesion experiments in the electrosensory system, however, suggest an alternative possibility. Inactivations of different maps of the first-order electrosensory nucleus in electric fish, the electrosensory lateral line lobe, resulted in markedly different behavioral deficits. The centromedial map is both necessary and sufficient for a particular electrolocation behavior, the jamming avoidance response, whereas it does not affect the communicative response to external electric signals. Conversely, the lateral map does not affect the jamming avoidance response but is necessary and sufficient to evoke communication behavior. Because the premotor pathways controlling the two behaviors in these fish appear to be separated as well, this system illustrates that sensory–motor control of different behaviors can occur in strictly segregated channels from the sensory input of the brain all through to its motor output. This might reflect an early evolutionary stage where multiplication of brain maps can satisfy the demand on processing a wider range of sensory signals ensuing from an enlarged behavioral repertoire, and bridging across maps is not yet required.

Visual constraints in foraging bumblebees: Flower size and color affect search time and flight behavior

In optimal foraging theory, search time is a key variable defining the value of a prey type. But the sensory-perceptual processes that constrain the search for food have rarely been considered. Here we evaluate the flight behavior of bumblebees (Bombus terrestris) searching for artificial flowers of various sizes and colors. When flowers were large, search times correlated well with the color contrast of the targets with their green foliage-type background, as predicted by a model of color opponent coding using inputs from the bees' UV, blue, and green receptors. Targets that made poor color contrast with their backdrop, such as white, UV-reflecting ones, or red flowers, took longest to detect, even though brightness contrast with the background was pronounced. When searching for small targets, bees changed their strategy in several ways. They flew significantly slower and closer to the ground, so increasing the minimum detectable area subtended by an object on the ground. In addition, they used a different neuronal channel for flower detection. Instead of color contrast, they used only the green receptor signal for detection. We relate these findings to temporal and spatial limitations of different neuronal channels involved in stimulus detection and recognition. Thus, foraging speed may not be limited only by factors such as prey density, flight energetics, and scramble competition. Our results show that understanding the behavioral ecology of foraging can substantially gain from knowledge about mechanisms of visual information processing.

PartsList: a web-based system for dynamically ranking protein folds based on disparate attributes, including whole-genome expression and interaction information

As the number of protein folds is quite limited, a mode of analysis that will be increasingly common in the future, especially with the advent of structural genomics, is to survey and re-survey the finite parts list of folds from an expanding number of perspectives. We have developed a new resource, called PartsList, that lets one dynamically perform these comparative fold surveys. It is available on the web at http://bioinfo.mbb.yale.edu/partslist and http://www.partslist.org. The system is based on the existing fold classifications and functions as a form of companion annotation for them, providing ‘global views’ of many already completed fold surveys. The central idea in the system is that of comparison through ranking; PartsList will rank the approximately 420 folds based on more than 180 attributes. These include: (i) occurrence in a number of completely sequenced genomes (e.g. it will show the most common folds in the worm versus yeast); (ii) occurrence in the structure databank (e.g. most common folds in the PDB); (iii) both absolute and relative gene expression information (e.g. most changing folds in expression over the cell cycle); (iv) protein–protein interactions, based on experimental data in yeast and comprehensive PDB surveys (e.g. most interacting fold); (v) sensitivity to inserted transposons; (vi) the number of functions associated with the fold (e.g. most multi-functional folds); (vii) amino acid composition (e.g. most Cys-rich folds); (viii) protein motions (e.g. most mobile folds); and (ix) the level of similarity based on a comprehensive set of structural alignments (e.g. most structurally variable folds). The integration of whole-genome expression and protein–protein interaction data with structural information is a particularly novel feature of our system. We provide three ways of visualizing the rankings: a profiler emphasizing the progression of high and low ranks across many pre-selected attributes, a dynamic comparer for custom comparisons and a numerical rankings correlator. These allow one to directly compare very different attributes of a fold (e.g. expression level, genome occurrence and maximum motion) in the uniform numerical format of ranks. This uniform framework, in turn, highlights the way that the frequency of many of the attributes falls off with approximate power-law behavior (i.e. according to V–b, for attribute value V and constant exponent b), with a few folds having large values and most having small values.

Linear and nonlinear pathways of spectral information transmission in the cochlear nucleus

At the level of the cochlear nucleus (CN), the auditory pathway divides into several parallel circuits, each of which provides a different representation of the acoustic signal. Here, the representation of the power spectrum of an acoustic signal is analyzed for two CN principal cells—chopper neurons of the ventral CN and type IV neurons of the dorsal CN. The analysis is based on a weighting function model that relates the discharge rate of a neuron to first- and second-order transformations of the power spectrum. In chopper neurons, the transformation of spectral level into rate is a linear (i.e., first-order) or nearly linear function. This transformation is a predominantly excitatory process involving multiple frequency components, centered in a narrow frequency range about best frequency, that usually are processed independently of each other. In contrast, type IV neurons encode spectral information linearly only near threshold. At higher stimulus levels, these neurons are strongly inhibited by spectral notches, a behavior that cannot be explained by level transformations of first- or second-order. Type IV weighting functions reveal complex excitatory and inhibitory interactions that involve frequency components spanning a wider range than that seen in choppers. These findings suggest that chopper and type IV neurons form parallel pathways of spectral information transmission that are governed by two different mechanisms. Although choppers use a predominantly linear mechanism to transmit tonotopic representations of spectra, type IV neurons use highly nonlinear processes to signal the presence of wide-band spectral features.