Organizational stressors and basic psychological needs: The mediating role of athletes' appraisal mechanisms.

This article reports the first study to quantitatively examine the relationships between the demands encountered by athletes that are associated with the organization within which they are operating, cognitive appraisals, and basic psychological need experiences. Three hundred and fifteen high-level British athletes completed a multisection questionnaire which assessed each of the aforementioned constructs. A series of path analyses provided valuable insight into the way in which the three dimensions (ie, frequency, intensity, and duration) of five organizational stressor categories were evaluated by athletes and, in turn, how such threat or challenge appraisals predicted feelings of need satisfaction and need frustration. Moreover, cognitive stress appraisals were found to mediate the relationship between organizational stressors and psychological need experiences. The role of secondary control appraisals was also explored and found to mediate the relationship between primary cognitive appraisals and basic psychological need experiences. Study limitations, proposed future research directions, and the implications of the findings for applied practitioners are discussed.

Effects of coach leadership and coach-athlete relationship on collective efficacy.

The study examined the independent and combined effects of coach leadership and coaching relationships on team efficacy. A total of 150 sport performers from football teams across a range of competitive levels completed a multisection self-report instrument to assess their individual perceptions of the level of collective efficacy, the type of coach leadership, and the quality of the coach-athlete relationship. Multiple regression analyses revealed that perceptions of both coach leadership and the coach-athlete relationship predicted variance in team efficacy. Overall, the findings suggest that the quality of coach-athlete relationships added to the prediction of individuals' collective efficacy beyond what was predicted by coaches' behaviors of leadership alone. Limitations and future research directions are discussed.

On parsing the neural code in the prefrontal cortex of primates using principal dynamic modes.

Nonlinear modeling of multi-input multi-output (MIMO) neuronal systems using Principal Dynamic Modes (PDMs) provides a novel method for analyzing the functional connectivity between neuronal groups. This paper presents the PDM-based modeling methodology and initial results from actual multi-unit recordings in the prefrontal cortex of non-human primates. We used the PDMs to analyze the dynamic transformations of spike train activity from Layer 2 (input) to Layer 5 (output) of the prefrontal cortex in primates performing a Delayed-Match-to-Sample task. The PDM-based models reduce the complexity of representing large-scale neural MIMO systems that involve large numbers of neurons, and also offer the prospect of improved biological/physiological interpretation of the obtained models. PDM analysis of neuronal connectivity in this system revealed "input-output channels of communication" corresponding to specific bands of neural rhythms that quantify the relative importance of these frequency-specific PDMs across a variety of different tasks. We found that behavioral performance during the Delayed-Match-to-Sample task (correct vs. incorrect outcome) was associated with differential activation of frequency-specific PDMs in the prefrontal cortex.

Design of optimal stimulation patterns for neuronal ensembles based on Volterra-type hierarchical modeling.

This paper presents a general methodology for the optimal design of stimulation patterns applied to neuronal ensembles in order to elicit a desired effect. The methodology follows a variant of the hierarchical Volterra modeling approach that utilizes input-output data to construct predictive models that describe the effects of interactions among multiple input events in an ascending order of interaction complexity. The illustrative example presented in this paper concerns the multi-unit activity of CA1 neurons in the hippocampus of a rodent performing a learned delayed-nonmatch-to-sample (DNMS) task. The multi-unit activity of the hippocampal CA1 neurons is recorded via chronically implanted multi-electrode arrays during this task. The obtained model quantifies the likelihood of having correct performance of the specific task for a given multi-unit (spatiotemporal) activity pattern of a CA1 neuronal ensemble during the 'sample presentation' phase of the DNMS task. The model can be used to determine computationally (off-line) the 'optimal' multi-unit stimulation pattern that maximizes the likelihood of inducing the correct performance of the DNMS task. Our working hypothesis is that application of this optimal stimulation pattern will enhance performance of the DNMS task due to enhancement of memory formation and storage during the 'sample presentation' phase of the task.

Dynamic nonlinear modeling of interactions between neuronal ensembles using principal dynamic modes.

We present a novel methodology for modeling the interactions between neuronal ensembles that utilizes the concept of Principal Dynamic Modes (PDM) and their associated nonlinear functions (ANF). This new approach seeks to reduce the complexity of the multi-input/multi-output (MIMO) model of the interactions between neuronal ensembles--an issue of critical practical importance in scaling up the MIMO models to incorporate hundreds (or even thousands) of input-output neurons. Global PDMs were extracted from the data using estimated first-order and second-order kernels and singular value decomposition (SVD). These global PDMs represent an efficient "coordinate system" for the representation of the MIMO model. The ANFs of the PDMs are estimated from the histograms of the combinations of PDM output values that lead to output spikes. For initial testing and validation of this approach, we applied it to a set of data collected at the pre-frontal cortex of a non-human primate during a behavioral task (Delayed Match-to-Sample). Recorded spike trains from Layer-2 neurons were viewed as the "inputs" and from Layer-5 neurons as the outputs. Model prediction performance was evaluated by means of computed Receiver Operating Characteristic (ROC) curves. The results indicate that this methodology may greatly reduce the complexity of the MIMO model without significant degradation of performance.

Restorative encoding memory integrative neural device: "REMIND".

Construction and application of a neural prosthesis device that enhances existing and replaces lost memory capacity in humans is the focus of research described here in rodents. A unique approach for the analysis and application of neural population firing has been developed to decipher the pattern in which information is successfully encoded by the hippocampus where mnemonic accuracy is critical. A nonlinear dynamic multi-input multi-output (MIMO) model is utilized to extract memory relevant firing patterns in CA3 and CA1 and to predict online what the consequences of the encoded firing patterns reflect for subsequent information retrieval for successful performance of delayed-nonmatch-to-sample (DNMS) memory task in rodents. The MIMO model has been tested successfully in a number of different contexts, each of which produced improved performance by a) utilizing online predicted codes to regulate task difficulty, b) employing electrical stimulation of CA1 output areas in the same pattern as successful cell firing, c) employing electrical stimulation to recover cell firing compromised by pharmacological agents and d) transferring and improving performance in naïve animals using the same stimulation patterns that are effective in fully trained animals. The results in rodents formed the basis for extension of the MIMO model to nonhuman primates in the same type of memory task that is now being tested in the last step prior to its application in humans.

Neural correlates of fast pupil dilation in nonhuman primates: relation to behavioral performance and cognitive workload.

Pupil dilation in humans has been previously shown to correlate with cognitive workload, whereby increased frequency of dilation is associated with increased degree of difficulty of a task. It has been suggested that frontal oculomotor brain areas control cognitively related pupil dilations, but this has not been confirmed due to lack of animal models of cognitive workload and task-related pupil dilation. This is the first report of a wavelet analysis applied to continuous measures of pupil size used to detect the onset of abrupt pupil dilations and the frequency of those dilations in nonhuman primates (NHPs) performing a trial-unique delayed-match-to-sample (DMS) task. A unique finding shows that electrophysiological recordings in the same animals revealed firing of neurons in frontal cortex correlated to different components of pupil dilation during task performance. It is further demonstrated that the frequency of fast pupil dilations (but not rate of eye movements) correlated with cognitive workload during task performance. Such correlations suggest that frontal neuron encoding of pupil dilation provides critical feedback to other brain areas involved in the processing of complex visual information.

The encoding of cocaine vs. natural rewards in the striatum of nonhuman primates: categories with different activations.

The behavioral and motivational changes that result from use of abused substances depend upon activation of neuronal populations in the reward centers of the brain, located primarily in the corpus striatum in primates. To gain insight into the cellular mechanisms through which abused drugs reinforce behavior in the primate brain, changes in firing of neurons in the ventral (VStr, nucleus accumbens) and dorsal (DStr, caudate-putamen) striatum to "natural" (juice) vs. drug (i.v. cocaine) rewards were examined in four rhesus monkeys performing a visual Go-Nogo decision task. Task-related striatal neurons increased firing to one or more of the specific events that occurred within a trial represented by (1) Target stimuli (Go trials) or (2) Nogotarget stimuli (Nogo trials), and (3) Reward delivery for correct performance. These three cell populations were further subdivided into categories that reflected firing exclusively on one or the other type of signaled reward (juice or cocaine) trial (20%-30% of all cells), or, a second subpopulation that fired on both (cocaine and juice) types of rewarded trial (50%). Results show that neurons in the primate striatum encoded cocaine-rewarded trials similar to juice-rewarded trials, except for (1) increased firing on cocaine-rewarded trials, (2) prolonged activation during delivery of i.v. cocaine infusion, and (3) differential firing in ventral (VStr cells) vs. dorsal (DStr cells) striatum cocaine-rewarded trials. Reciprocal activations of antithetic subpopulations of cells during different temporal intervals within the same trial suggest a functional interaction between processes that encode drug and natural rewards in the primate brain.

Mechanisms underlying cognitive enhancement and reversal of cognitive deficits in nonhuman primates by the ampakine CX717.

RATIONALE: Performance of cognitive tasks in nonhuman primates (NHPs) requires specific brain regions to make decisions under different degrees of difficulty or "cognitive load." OBJECTIVE: Local cerebral metabolic activity ([18F]FDG PET imaging) in dorsolateral prefrontal cortex (DLPFC), medial temporal lobe (MTL), and dorsal striatum (DStr) is examined in NHPs performing a delayed-match-to-sample (DMS) task with variable degrees of cognitive load. MATERIALS AND METHODS: Correlations between cognitive load and degree of brain metabolic activity were obtained with respect to the influence of the ampakine CX717 (Cortex Pharmaceuticals), using brain imaging and recordings of neuronal activity in NHPs and measures of intracellular calcium release in rat hippocampal slices. RESULTS: Activation of DLPFC, MTL, and DStr reflected changes in performance related to cognitive load within the DMS task and were engaged primarily on high load trials. Similar increased activation patterns and improved performance were also observed following administration of CX717. Sleep deprivation in NHPs produced impaired performance and reductions in brain activation which was reversed by CX717. One potential basis for this facilitation of cognition by CX717 was increased firing of task-specific hippocampal cells. Synaptic mechanisms affected by CX717 were examined in rat hippocampal slices which showed that N-methyl-D-aspartic acid-mediated release of intracellular calcium was reduced in slices from sleep-deprived rats and reversed by application of CX717 to the bathing medium. CONCLUSIONS: The findings provide insight into how cognition is enhanced by CX717 in terms of brain, and underlying neural, processes that are activated on high vs. low cognitive load trials.

A pilot study of a Mediterranean-type diet intervention in female patients with rheumatoid arthritis living in areas of social deprivation in Glasgow.

BACKGROUND: A Mediterranean-type diet rich in fish, fruit and vegetables and low in saturated fats has been associated with health benefits, including improved cardiovascular profile and benefit in RA. OBJECTIVE: To overcome obstacles to healthy eating by a community-based intervention promoting a Mediterranean-type diet in patients with RA living in socially deprived areas of Glasgow. METHODS: 130 female patients with RA aged 30-70 years (median 55), disease duration 8 years were recruited from three hospital sites. The intervention group (n = 75) attended weekly 2-hour sessions for 6 weeks in the local community, including hands-on cooking classes backed up with written information. The control group (n = 55) were given dietary written information only. Both groups completed food frequency questionnaires (FFQs), and clinical and laboratory measures were assessed at baseline, 3 and 6 months. RESULTS: Significant benefit was shown in the intervention group compared with controls for patient global assessment at 6 months (p = 0.002), pain score at 3 and 6 months (p = 0.011 and 0.049), early morning stiffness at 6 months (p = 0.041) and Health Assessment Questionnaire score at 3 months (p = 0.03). Analysis of the FFQs showed significant increases in weekly total fruit, vegetable and legume consumption and improvement in the ratio of monounsaturated:saturated fat intake and systolic BP in the intervention group only. The cooking classes were positively received by patients and tutors; cost/patient for the 6 week course was 84 pounds (124 euro). CONCLUSIONS: Results demonstrate that a 6 week intervention can improve consumption of healthier foods. If implemented more widely it may prove a popular, inexpensive and useful adjunct to other RA treatment.

The synthetic cannabinoid HU210 induces spatial memory deficits and suppresses hippocampal firing rate in rats.

BACKGROUND AND PURPOSE: Previous work implied that the hippocampal cannabinoid system was particularly important in some forms of learning, but direct evidence for this hypothesis is scarce. We therefore assessed the effects of the synthetic cannabinoid HU210 on memory and hippocampal activity. EXPERIMENTAL APPROACH: HU210 (100 microg kg(-1)) was administered intraperitoneally to rats under three experimental conditions. One group of animals were pre-trained in spatial working memory using a delayed-matching-to-position task and effects of HU210 were assessed in a within-subject design. In another, rats were injected before acquisition learning of a spatial reference memory task with constant platform location. Finally, a separate group of animals was implanted with electrode bundles in CA1 and CA3 and single unit responses were isolated, before and after HU210 treatment. KEY RESULTS: HU210 treatment had no effect on working or short-term memory. Relative to its control Tween 80, deficits in acquisition of a reference memory version of the water maze were obtained, along with drug-related effects on anxiety, motor activity and spatial learning. Deficits were not reversed by the CB(1) receptor antagonists SR141716A (3 mg kg(-1)) or AM281 (1.5 mg kg(-1)). Single unit recordings from principal neurons in hippocampal CA3 and CA1 confirmed HU210-induced attenuation of the overall firing activity lowering both the number of complex spikes fired and the occurrence of bursts. CONCLUSIONS AND IMPLICATIONS: These data provide the first direct evidence that the underlying mechanism for the spatial memory deficits induced by HU210 in rats is the accompanying abnormality in hippocampal cell firing.

Vesicular glutamate transporter VGLUT2 expression levels control quantal size and neuropathic pain.

Uptake of L-glutamate into synaptic vesicles is mediated by vesicular glutamate transporters (VGLUTs). Three transporters (VGLUT1-VGLUT3) are expressed in the mammalian CNS, with partial overlapping expression patterns, and VGLUT2 is the most abundantly expressed paralog in the thalamus, midbrain, and brainstem. Previous studies have shown that VGLUT1 is necessary for glutamatergic transmission in the hippocampus, but the role of VGLUT2 in excitatory transmission is unexplored in glutamatergic neurons and in vivo. We examined the electrophysiological and behavioral consequences of loss of either one or both alleles of VGLUT2. We show that targeted deletion of VGLUT2 in mice causes perinatal lethality and a 95% reduction in evoked glutamatergic responses in thalamic neurons, although hippocampal synapses function normally. Behavioral analysis of heterozygous VGLUT2 mice showed unchanged motor function, learning and memory, acute nociception, and inflammatory pain, but acquisition of neuropathic pain, maintenance of conditioned taste aversion, and defensive marble burying were all impaired. Reduction or loss of VGLUT2 in heterozygous and homozygous VGLUT2 knock-outs led to a graded reduction in the amplitude of the postsynaptic response to single-vesicle fusion in thalamic neurons, indicating that the vesicular VGLUT content is critically important for quantal size and demonstrating that VGLUT2-mediated reduction of excitatory drive affects specific forms of sensory processing.

Behaviorally relevant endocannabinoid action in hippocampus: dependence on temporal summation of multiple inputs.

Endocannabinoids have been shown to mediate depolarization-induced suppression of GABAergic inhibition (DSI), possibly via release and retrograde diffusion following moderate to severe depolarization of hippocampal pyramidal neurons. However, it is not clear how hippocampal neurons, which have relatively low firing rates in vivo, achieve the degree of depolarization required to release endocannabinoids. Here it is demonstrated that DSI is not dependent on the occurrence of action potentials in the postsynaptic neuron, but is mediated by depolarization-induced calcium entry via voltage-controlled calcium channels (VCCs). The optimal level of calcium entry, and subsequent DSI, are directly related to the frequency of depolarizing pulses, which differs between immature and adult hippocampus. However, it is shown via modeled spike train inputs that the frequency dependence of DSI is overcome if two or more convergent spike trains from different neurons with normal in vivo firing rates converge and overlap in time. In these modeled circumstances, endocannabinoid-mediated DSI occurs most often when converging synaptic inputs from multiple neurons fire in synchrony to allow temporal summation of local membrane events in postsynaptic cells to exceed threshold for calcium entry. It is therefore possible that such suppression of inhibition would only occur during the time that recipient hippocampal neurons receive multiple coincident excitatory synaptic inputs.

Lack of radiological and clinical benefit over two years of low dose prednisolone for rheumatoid arthritis: results of a randomised controlled trial.

BACKGROUND: Evidence for disease modifying activity of low dose corticosteroid treatment in rheumatoid arthritis is contradictory. Studies showing radiological benefit suggest that continued treatment is required to sustain the effect. OBJECTIVE: To evaluate the effect of low dose oral prednisolone in early rheumatoid arthritis on disease activity over two years. DESIGN: Double blind placebo controlled trial. METHODS: Patients with rheumatoid arthritis, duration <3 years (n = 167), were started on a disease modifying antirheumatic drug (DMARD; sulphasalazine) and allocated by stratified randomisation to prednisolone 7 mg/day or placebo. Primary outcome measure was radiological damage, assessed by the modified Sharp method. Clinical benefit was a secondary outcome. A proactive approach to identifying and treating corticosteroid adverse events was adopted. Patients who discontinued sulphasalazine were offered an alternative DMARD. RESULTS: 90 of 257 patients eligible for the study refused to participate (more women than men). Of those enrolled, 84% were seropositive for rheumatoid factor, median age 56 years, median disease duration 12 months, female to male ratio 1.8:1. Prednisolone was given to 84 patients; of these 73% continued prednisolone and 70% sulphasalazine at 2 years. Of the 83 patients on placebo, 80% continued placebo and 64% sulphasalazine at 2 years. There were no significant differences in radiological score or clinical and laboratory measures at 0 and 2 years. CONCLUSIONS: Low dose prednisolone conferred no radiological or clinical benefit on patients maintained on a DMARD over two years. Low dose corticosteroids have no role in the routine management of rheumatoid arthritis treated with conventional disease modifying drugs.

Illiteracy in rheumatoid arthritis patients as determined by the Rapid Estimate of Adult Literacy in Medicine (REALM) score.

OBJECTIVES: To determine the prevalence of illiteracy in a cohort of rheumatoid arthritis (RA) patients and the impact of illiteracy on disease severity and function. METHODS: We performed a prospective cross-sectional study with case record review of 127 consecutive patients with RA attending one centre. All patients completed the Rapid Estimate of Adult Literacy in Medicine (REALM) screening test. This 66-word recognition test provides an estimate of reading level in less than 3 min. Demographic data were collected by interview and case record review. Function was assessed with the Health Assessment Questionnaire (HAQ) and depression with the Hospital Anxiety and Depression (HAD) scale, both sent prior to clinic attendance. Social deprivation was assessed with the Carstairs index. RESULTS: Four patients refused to participate. Of these, three stated they were unable to read. Ninety-seven women and 26 men agreed to be interviewed. All but two were Caucasian. Median age was 56 yr (range 19-77 yr) and median disease duration was 10 yr (range 1-60 yr). Median number of previous disease-modifying anti-rheumatic drugs (DMARDs) was two. Eighteen (15%) patients were functionally illiterate, with a REALM score of less than 60. Sex, age, disease duration and numbers of joint replacements and previous DMARDs were not influenced by illiteracy. Illiteracy led to more anxiety (P=0.011), but did not affect HAQ score (P>0.5). Illiteracy was more common in the deprived (P=0.0064). Illiterate patients had three times more hospital visits compared with age- and sex-matched RA controls over the previous 12 months. CONCLUSIONS: One in six of our patient population are illiterate and would struggle to cope with patient education materials and prescription labels. These patients had significantly more hospital visits but equal function, suggesting that additional resources be directed towards these individuals. The REALM test is quick and easy to administer and allows us to identify patients who may require more appropriate literature.

Hedgehog signalling is required for maintenance of myf5 and myoD expression and timely terminal differentiation in zebrafish adaxial myogenesis.

Hedgehog proteins have been implicated in the control of myogenesis in the medial vertebrate somite. In the mouse, normal epaxial expression of the myogenic transcription factor gene myf5 is dependent on Sonic hedgehog. Here we examine in zebrafish the interaction between Hedgehog signals, the expression of myoD family genes, including the newly cloned zebrafish myf5, and slow myogenesis. We show that Sonic hedgehog is necessary for normal expression of both myf5 and myoD in adaxial slow muscle precursors, but not in lateral paraxial mesoderm. Expression of both genes is initiated normally in rostral presomitic mesoderm in sonic you mutants, which lack all Sonic hedgehog. Similar initiation continues during tailbud outgrowth when the cells forming caudal somites are generated. However, adaxial cells in sonic you embryos are delayed in terminal differentiation and caudal adaxial cells fail to maintain myogenic regulatory factor expression. Despite these defects, other signals are able to maintain, or reinitiate, some slow muscle development in sonic you mutants. In the cyclops mutant, the absence of floorplate-derived Tiggywinkle hedgehog and Sonic hedgehog has no discernible effect on slow adaxial myogenesis. Similarly, the absence of notochord-derived Sonic hedgehog and Echidna hedgehog in mutants lacking notochord delays, but does not prevent, adaxial slow muscle development. In contrast, removal of both Sonic hedgehog and a floorplate signal, probably Tiggywinkle hedgehog, from the embryonic midline in cyclops;sonic you double mutants essentially abolishes slow myogenesis. We conclude that several midline signals, likely to be various Hedgehogs, collaborate to maintain adaxial slow myogenesis in the zebrafish embryo. Moreover, the data demonstrate that, in the absence of this required Hedgehog signalling, expression of myf5 and myoD is insufficient to commit cells to adaxial myogenesis.

Muscular expressions: profiling genes in complex tissues.

Gene-expression profiling has yielded important information about simple systems, but complex tissues have not yet been widely profiled. Four recent studies of mammalian skeletal muscles have added to the catalogs of their gene expression differences, but have yet to lead to better understanding of the molecular processes underlying their physiological differences.

Cannabinoid and kappa opioid receptors reduce potassium K current via activation of G(s) proteins in cultured hippocampal neurons.

The current study showed that potassium K current (I(K)), which is evoked at depolarizing potentials between -30 and +40 mV in cultured hippocampal neurons, was significantly reduced by exposure to the CB1 cannabinoid receptor agonist WIN 55,212-2 (WIN-2). WIN-2 (20-40 nM) produced an average 45% decrease in I(K) amplitude across all voltage steps, which was prevented by SR141716A, the CB1 receptor antagonist. The cannabinoid receptor has previously been shown to be G(i/o) protein-linked to several cellular processes; however, the decrease in I(K) was unaffected by modulators of G(i/o) proteins and agents that alter levels of protein kinase A. In contrast, CB1 receptor-mediated or direct activation of G(s) proteins with cholera toxin (CTX) produced the same decrease in I(K) amplitude as WIN-2, and the latter was blocked in CTX-treated cells. G(s) protein inhibition via GDPbetaS also eliminated the effects of WIN-2 on I(K). Consistent with this outcome, activation of protein kinase C (PKC) by arachidonic acid produced similar effects to WIN-2 and CTX. Kappa opioid receptor agonists, which also reduce I(K) amplitude via G(s) proteins, were compared with WIN-2 actions on I(K.) The kappa receptor agonist U50,488 reduced I(K) amplitude in the same manner as WIN-2, while the kappa receptor antagonist, nor-binaltorphimine, actually increased I(K) amplitude and significantly reduced the effect of co-administered WIN-2. The results indicate that CB1 and kappa receptor activation is additive with respect to I(K) amplitude, suggesting that CB1 and kappa receptors share a common G(s) protein signaling pathway involving PKC.

Large-scale analysis of gene expression changes during acute and chronic exposure to [Delta]9-THC in rats.

Large-scale cDNA microarrays were employed to assess transient changes in gene expression levels following acute and chronic exposure to cannabinoids in rats. A total of 24,456 cDNA clones were randomly selected from a rat brain cDNA library, amplified by PCR, and arrayed at high density to investigate differential gene expression profiles following acute (24 h), intermediate (7 days), and chronic (21 days) exposure to Delta(9)-tetrahydrocannabinol (Delta(9)-THC), the psychoactive ingredient of marijuana. Hippocampal mRNA probes labeled with (33)P obtained from both vehicle and Delta(9)-THC-treated animals were hybridized with identical cDNA microarrays. Results revealed a total of 49 different genes altered by Delta(9)-THC exposure; of these, 28 were identified, 10 had homologies to expressed sequence tags (ESTs), and 11 had no homology to known sequences in the GenBank database. Chronic or acute cannabinoid receptor activation altered expression of several genes (i.e., prostaglandin D synthase, calmodulin) involved in biochemical cascades of cannabinoid synthesis or cannabinoid effector systems. Other genes [i.e., neural cell adhesion molecule (NCAM), myelin basic protein], whose relation to cannabinoid system function was not immediately obvious, were also significantly altered. Verification of the changes obtained with the large-scale screen was determined by RNA dot blots in different groups of animals treated the same as those in the large-scale screen. Results are discussed in terms of the different types of genes affected at different times during chronic Delta(9)-THC exposure.