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Biomedical subjects

J W Grimm

Publications and source records attributed to J W Grimm.

18 recordsLinked to original sources
PubMed2005

Improved daily precipitation nitrate and ammonium concentration models for the Chesapeake Bay Watershed.

Daily precipitation nitrate and ammonium concentration models were developed for the Chesapeake Bay Watershed (USA) using a linear least-squares regression approach and precipitation chemistry data from 29 National Atmospheric Deposition Program/National Trends Network (NADP/NTN) sites. Only weekly samples that comprised a single precipitation event were used in model development. The most significant variables in both ammonium and nitrate models included: precipitation volume, the number of days since the last event, a measure of seasonality, latitude, and the proportion of land within 8km covered by forest or devoted to industry and transportation. Additional variables included in the nitrate model were the proportion of land within 0.8km covered by water and/or forest. Local and regional ammonia and nitrogen oxide emissions were not as well correlated as land cover. Modeled concentrations compared very well with event chemistry data collected at six NADP/AirMoN sites within the Chesapeake Bay Watershed. Wet deposition estimates were also consistent with observed deposition at selected sites. Accurately describing the spatial distribution of precipitation volume throughout the watershed is important in providing critical estimates of wet-fall deposition of ammonium and nitrate.

Air Pollutants↗
PubMed2002

Effect of cocaine and sucrose withdrawal period on extinction behavior, cue-induced reinstatement, and protein levels of the dopamine transporter and tyrosine hydroxylase in limbic and cortical areas in rats.

Lever pressing during tests for resistance to extinction and cue-induced reinstatement of cocaine seeking in rats progressively increases over the first 2 months of withdrawal. In the present report, we investigated the generality of these findings in rats trained to self-administer sucrose, a non-drug reinforcer. We also examined whether the time-dependent changes in cocaine seeking correlate with the levels of the dopamine transporter (DAT) and tyrosine hydroxylase (TH) proteins in the amygdala, nucleus accumbens, prefrontal cortex and orbitofrontal cortex. Rats were trained to self-administer cocaine (0.5 mg/kg/i.v. infusion) or 10% sucrose (0.2 ml/infusion into a liquid drop receptacle) for 10 days (6 h/day); each reward delivery was paired with a tone+light cue. Tests for cocaine seeking were conducted following 1 or 15 reward-free days. On the test day, rats were initially tested for resistance to extinction during 6-7 60-min extinction sessions in the absence of the tone-light cue, until they reached the extinction criterion of less than 15 responses/60 min. Subsequently, rats were tested for cue-induced reinstatement during a 60-min session in which each lever press led to a contingent presentation of the tone-light cue. Lever pressing during the tests for reward seeking was significantly greater on day 15 than on day 1 following withdrawal from both cocaine and sucrose self-administration training. The levels of DAT, but not TH, were greater in the prefrontal cortex of cocaine-trained rats than in sucrose-trained rats on both days 1 and 15 of withdrawal. The levels of DAT and TH in other brain areas were not altered following withdrawal from cocaine or sucrose self-administration. These data suggest that the withdrawal can modulate reward seeking of both drug and non-drug reinforcers, and that alterations in DAT and TH levels in the brain regions examined do not mediate this effect.

Animals↗
PubMed2001

Decreased choline acetyltransferase immunoreactivity in discrete striatal subregions following chronic haloperidol in rats.

Neuronal loss within the basal ganglia has been hypothesized to play a role in movement disorders (e.g., tardive dyskinesia) that often occur following chronic neuroleptic treatment. Previous studies in animal models have provided some support to this possibility, but have not assessed regionally specific changes after chronic neuroleptic administration. The present study examined whether counts of neurons containing acetylcholine, described as large aspiny type II neurons, were altered in subregions of the corpus striatum and nucleus accumbens following chronic haloperidol administration in rats. Rats were administered haloperidol decanoate (21 mg/kg, i.m.) or vehicle every third week for 24 weeks. Following 4 weeks of withdrawal from the drug, predefined regions were examined for choline acetyltransferase (ChAT) immunoreactive (ir) cells. Compared to the vehicle group, the haloperidol group showed significant reductions in ChAT-ir cell counts in the ventrolateral striatum, nucleus accumbens core, and nucleus accumbens lateral shell. No significant differences were found in the other regions examined: dorsolateral striatum, dorsomedial striatum, ventromedial striatum, nucleus accumbens medial shell, and horizontal limb of the diagonal band. These findings indicate that there may be regionally specific alterations in ChAT-ir cells following chronic haloperidol treatment, supporting previous hypotheses of striatal cholinergic cell loss resulting from chronic neuroleptic treatment. More importantly, the regions affected (ventrolateral striatum and nucleus accumbens) are critical in the regulation of oral movements, thus suggesting that alterations in cholinergic cell activity, and perhaps actual loss of cholinergic cells in these regions, may be important in the manifestation of late-onset oral dyskinesia.

Acetylcholine↗
PubMed2001

Dopamine, but not glutamate, receptor blockade in the basolateral amygdala attenuates conditioned reward in a rat model of relapse to cocaine-seeking behavior.

RATIONALE: Following chronic cocaine self-administration and extinction, lesions of the basolateral amygdala (BLA) will significantly attenuate responding for secondary reward (tone + light previously paired with cocaine), without disrupting lever responding for primary reward. However, the specific neurotransmitters involved in conditioned reinstatement remain to be determined. OBJECTIVE: In the present study, we examined possible receptor substrates of amygdalar regulation of conditioned reinstatement after chronic cocaine self-administration. METHODS: Rats were allowed 2 weeks of 3-h daily sessions of cocaine self-administration along a fixed ratio (FR) 1 schedule. After 1 week of daily 3-h extinction sessions in which no programmed consequences occurred, selective antagonists of glutamate or dopamine (DA) receptors were bilaterally infused at single doses into the BLA prior to testing for a cocaine-conditioned reward (tone + light). Following three more days of extinction trials, receptor antagonist effects on reinstatement of cocaine self-administration in the absence of the conditioned stimulus were determined. RESULTS: Infusion of an NMDA receptor antagonist (AP-5, 1.97 micrograms/side), a kainate/alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor antagonist (CNQX, 0.83 microgram/side), or both drugs together had no significant effects on conditioned reward or reinstatement of cocaine self-administration. In contrast, infusion of a DA D1 receptor antagonist (SCH-23390, 2 micrograms/side) or a combination of SCH-23390 and a DA D2/D3 receptor antagonist (raclopride, 5 micrograms/side) significantly reduced responding for conditioned reward, but did not affect cocaine self-administration. Raclopride alone was without effect on either test day. CONCLUSIONS: These results suggest that conditioned reinstatement of drug-seeking behavior is dependent on amygdalar D1 receptors.

2-Amino-5-phosphonovalerate↗
PubMed2001

Repeated lofexidine treatment attenuates stress-induced, but not drug cues-induced reinstatement of a heroin-cocaine mixture (speedball) seeking in rats.

Alpha-2 adrenoceptor agonists (lofexidine, clonidine) are used to alleviate short-term opioid withdrawal in humans. In rats, acute injections of these agents attenuate stress-induced reinstatement of heroin and cocaine seeking at time points that are beyond the acute drug withdrawal phase. Here, we studied whether exposure to lofexidine would attenuate reinstatement of a heroin-cocaine mixture (speedball) seeking induced by exposure to stress or to drug-associated cues. Rats were trained to lever press for speedball for 10 days, and the drug-reinforced behavior was then extinguished for 11 days in the presence (Experiment 1) or the absence (Experiment 2) of the drug cues. Subsequently, rats were tested for reinstatement of drug seeking after exposure to intermittent footshock stress (5-15 min; Experiment 1) or the drug cues (Experiment 2). Starting on day 7 of training, rats received daily injections of saline or lofexidine (0.1 or 0.2 mg/kg). Repeated lofexidine treatment significantly attenuated footshock-induced reinstatement, but did not alter drug cues-induced reinstatement of speedball seeking. In addition, lofexidine did not have a consistent effect on speedball self-administration and extinction behavior. Results extend previous reports with acute drug injections, indicating that lofexidine maintains its effect on stress-induced reinstatement after repeated treatment. The present data also suggest that the neurochemical events underlying stress- and drug cues-induced relapse are not identical.

Adrenergic alpha-Agonists↗
PubMed2000

Chronic haloperidol-induced alterations in pallidal GABA and striatal D(1)-mediated dopamine turnover as measured by dual probe microdialysis in rats.

Using dual probe microdialysis, assessment of extracellular neurotransmitter levels in the corpus striatum and globus pallidus was performed in ovariectomized and gonadally intact female, Sprague-Dawley rats following chronic (24 weeks) oral haloperidol administration. Vacuous chewing movements, an animal analog of orofacial dyskinesia, were also recorded at several time points during haloperidol administration and throughout the dialysis sampling session. Basal GABA levels were significantly elevated in the globus pallidus of haloperidol-treated rats compared with vehicle animals. Injection of the dopamine D(1) agonist dihydrexidine (3mg/kg, s.c.) decreased striatal dopamine levels in both vehicle and haloperidol-treated rats, with a larger decrease seen in haloperidol-treated rats. Furthermore, dihydrexidine reduced striatal 3,4-dihydroxyphenylacetic acid and homovanillic acid levels only in haloperidol-treated rats. Gonadal status had no effect on any neurochemical measure. Vacuous chewing movements were significantly elevated in haloperidol-treated groups by the sixth week of treatment, with higher counts seen in gonadally intact rats. Vacuous chewing movements were significantly elevated above baseline in all groups following dihydrexidine, with no differential effect of prior haloperidol treatment or gonadal status. These results indicate a tonic increase in pallidal GABA levels and a hypersensitivity of D(1)-mediated striatal dopamine and dopamine metabolite decreases following chronic haloperidol treatment. While not found to be correlated with neurochemical measures, the heightened vacuous chewing movements in gonadally intact vs ovariectomized rats may serve as a model of hormone-mediated differences in neuroleptic-induced oral dyskinesia.

Animals↗
PubMed2000

Dissociation of primary and secondary reward-relevant limbic nuclei in an animal model of relapse.

The neural substrates underlying relapse to drug-seeking behavior after chronic drug abuse may differ from those underlying immediate drug-taking behavior. In a model of relapse to drug-seeking behavior following chronic cocaine self-administration and prolonged extinction, we have previously shown that rats will significantly reinstate lever responding for either primary reward (cocaine) or secondary reward (tone + light stimulus previously paired with cocaine). In the present study, we utilized reversible inactivation of discrete brain nuclei with tetrodotoxin (TTX) in order to examine the neural substrates mediating primary and secondary cocaine reward in rats allowed two weeks of cocaine self-administration. After one week of daily extinction sessions, bilateral inactivation of the basolateral amygdala resulted in significant attenuation of lever pressing for a cocaine-conditioned reward (tone + light). Following three more days of extinction, bilateral TTX inactivation of the basolateral amygdala had no effect on the reinstatement of cocaine self-administration. In contrast, TTX inactivation of the nucleus accumbens produced the exact opposite effects, with significant blockade of primary reward (cocaine alone), but not secondary reward (tone + light). Thus, cocaine-conditioned reward is neuroanatomically dissociated from primary cocaine reward.

Amygdala↗
PubMed1999

The importance of a compound stimulus in conditioned drug-seeking behavior following one week of extinction from self-administered cocaine in rats.

Previous studies have demonstrated that conditioned stimuli can increase responding on a drug-associated lever after extinction from drug self-administration. The present study investigated singular stimuli (tone or light) or a compound stimulus (tone + light) for their ability to increase extinguished responding following chronic cocaine self-administration. Rats self-administered cocaine for 2 weeks on a fixed ratio (FR1) schedule of reinforcement, in which lever responding resulted in varied presentation of a tone, light, or tone + light combination. The rats were then exposed to 1 week of daily extinction sessions. Presentation of the tone + light on day 8 of extinction in the absence of cocaine reinforcement resulted in a significant increase in responding, while either stimulus component alone was much weaker or failed to produce any changes from extinction rates of responding. In addition, changing the duration of the single elements of the compound did not affect the magnitude of increased responding to the compound. Following three final extinction sessions, robust lever responding for cocaine infusions on day 12 of extinction was seen across all groups. These findings suggest that compound stimuli may be critical to fully activate drug-seeking behavior in conditions of craving and relapse following prolonged extinction.

Acoustic Stimulation↗
PubMed1999

Predicting relapse to cocaine-seeking behavior: a multiple regression approach.

Recovery of previously extinguished responding to stimuli paired with the administration of drugs of abuse is becoming a widely utilized animal model of relapse to drug-seeking behaviors. While this approach is useful for identifying factors such as conditioned stimuli that are associated with drug-seeking, it has not directly identified behaviors that might predict susceptibility to relapse. In this study, rats were initially screened for locomotor activity in response to a novel environment. Rats were then trained to self-administer cocaine. A stimulus light and tone were paired with each infusion of cocaine. After 14 days of self-administration (maintenance) rats underwent 7 days of extinction trials (extinction phase 1), in which responding yielded neither cocaine nor the presentation of the conditioned stimulus. After extinction phase 1, rats responded for presentations of the compound stimulus in the absence of cocaine (test day 1). Rats then underwent 3 more days of extinction (extinction phase 2). After extinction phase 2, rats were once again allowed to self-administer cocaine (test day 2) and received presentations of the compound stimulus. Hierarchical regression equations, utilizing data from locomotor screening and the average responding during maintenance and extinction phases 1 and 2, were then constructed in order to predict the magnitude of responding on test days 1 and 2. A model utilizing locomotor activity, maintenance responding and extinction phase 1 responding accounted for over 76% of the variance associated with responding on test day 1, with extinction phase 1 as best predictor. A further model indicated that locomotor activity was the best predictor of propensity to self-administer cocaine on test day 2. These regression models provide a novel approach to determining factors that may predict relapse to drug-seeking behaviors.

Animals↗
PubMed1998

Unique activation of extracellular striato-pallidal neurotransmitters in rats following acute risperidone.

The present study investigated the effects of the putative atypical antipsychotic drug (APD), risperidone, on striatal monoamine and pallidal gamma-aminobutyric acid (GABA) function using dual probe in vivo microdialysis. Risperidone (0.03, 0.3, 3 mg/kg) or vehicle was injected (s.c.) into female, Sprague-Dawley rats fitted with dual microdialysis probes in the striatum and the globus pallidus (GP). In the striatum, risperidone increased extracellular levels of dopamine (DA) and 3,4-dihydroxyphenylacetic acid (DOPAC) at all doses and the serotonin (5-HT) metabolite, 5-hydroxyindoleacetic acid (5-HIAA), at the highest dose. The increase in striatal DA was most pronounced at the lowest dose of risperidone; however, DOPAC showed a dose dependent increase. Risperidone at the medium and high doses significantly reduced extracellular GABA levels in the GP. Simultaneous measurement of limb rigidity during microdialysis showed that risperidone dose-dependently produced significant increases in horizontal bar test catalepsy and fore- and hindlimb paw retraction latencies. The current results suggest novel effects of risperidone on striatal DA release, while the pallidal GABA changes are similar to previous results obtained with the atypical antipsychotic drug, clozapine. Additionally, the behavioral results predict the clinical expression of extrapyramidal motor side effects at high doses. Overall, these results support an atypical profile of risperidone when compared with typical APDs, yet one with unique neurochemical and behavioral properties.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1998

Emergence of oral and locomotor activity in chronic haloperidol-treated rats following cortical N-methyl-D-aspartate stimulation.

Neuroleptic-induced orofacial movements in rats have been widely utilized as an animal model of tardive dyskinesia (TD). The present study investigated the role of the oral motor cortex in these movements by applying direct cortical stimulation in rats exposed to chronic haloperidol. Rats received depot i.m. injections of haloperidol decanoate or sesame oil vehicle every 3 weeks (10 rats per group). After 24 weeks of injections and a 3-week withdrawal period, bilateral guide cannulae were implanted into the primary oral motor cortex. After a 1-week recovery, bilateral microinfusions of saline vehicle followed by 1, 3, and 10 mM N-methyl-D-aspartate (NMDA) were given and observations of oral activity, locomotion, rearing, and grooming were recorded. Haloperidol-treated rats displayed a significant emergence of NMDA stimulated oral activity (nondirected oral movements, oral tremor, audible teeth grinding, and directed oral movements). In addition, rearing and locomotion were significantly elevated in these animals. In contrast to haloperidol-treated rats, sesame oil-treated rats showed no significant emergence of any motor activity. These results suggest that chronic haloperidol administration alters primary motor cortex efferents, and that this effect may be a factor in the manifestation of chronic neuroleptic induced motor side effects, such as TD.

Animals↗
PubMed1997

Cocaine self-administration in ovariectomized rats is predicted by response to novelty, attenuated by 17-beta estradiol, and associated with abnormal vaginal cytology.

Parameters of cocaine self-administration behavior and vaginal cytological changes were assessed in ovariectomized rats during and after chronic self-administration. Response to novelty as measured by locomotor activity was found to correlate with cocaine self-administration on both fixed ratio (FR) and progressive ratio (PR) schedules of reinforcement. Chronic 17-beta estradiol (E2) replacement did not affect cocaine self-administration on FR or PR schedules of reinforcement. Acute E2 administration decreased cocaine self-administration on a PR schedule of reinforcement on the day of and on the two days following hormone treatment. Finally, the proliferation of vaginal epithelia following acute E2 was potentiated in rats both during cocaine self-administration and 30 days into withdrawal when compared with non-drug-exposed animals. These results identify response to novelty as a behavioral index predictive of cocaine self-administration liability in female rats and additionally provide evidence of psychostimulant-hormonal interactions highly relevant to female behavior and physiology.

Animals↗
PubMed1995

Tolerance-like attenuation to contingent and noncontingent cocaine-induced elevation of extracellular dopamine in the ventral striatum following 7 days of withdrawal from chronic treatment.

Time-dependent changes in mesolimbic dopamine (DA) function are believed to play a role in behavioral sensitization and drug craving experienced during withdrawal from chronic cocaine administration. The present study utilized intravenous (IV) cocaine self-administration coupled with intracranial microdialysis in rats to investigate time dependent changes during withdrawal from chronic cocaine exposure. Following 2 weeks of IV cocaine self-administration, rats were allowed contingent access to cocaine at 1 and 7 days of withdrawal while extracellular levels of DA were measured from the ventral striatum. A second group of animals received yoked, noncontingent cocaine for 2 weeks and were then administered noncontingent cocaine on days 1 and 7 of withdrawal. In addition, a third group of animals received 2 weeks of yoked saline followed by noncontingent cocaine 1 day after withdrawal. There were no significant differences between groups for the overall cocaine dosage or temporal pattern of infusions on days 1 and 7 of withdrawal. Basal extracellular DA concentrations did not differ between any treatment groups at either withdrawal time. Extracellular DA levels were increased throughout the session on both days; however, the increases at day 7 were significantly less than day 1 for both contingent and noncontingent conditions. DA overflow on day 1 did not differ between animals receiving chronic yoked cocaine or saline. These results suggest that tolerance-like attenuation to the DA-elevating effects of cocaine is not apparent early in withdrawal, but does develop by later time points.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1995

Surgical referrals as evidence of a de facto podiatric medical specialization.

The authors present evidence on the patterns and correlates of surgical referrals to podiatric physicians that suggests a surgical specialty now exists in podiatric medicine. The primary factors on which surgical specialization appears to be based are residency training, hospital medical staff membership, and increased hospital podiatric practice activity. Surgically specialized podiatric physicians tend to be younger, but such specialization is not related to either the gender or race of podiatric physicians.

Adult↗