Biomedical subjects

S H Nader

Publications and source records attributed to S H Nader.

5 recordsLinked to original sources

PubMed2001

Chronic cocaine-mediated changes in non-human primate nucleus accumbens gene expression.

Chronic cocaine use elicits changes in the pattern of gene expression within reinforcement-related, dopaminergic regions. cDNA hybridization arrays were used to illuminate cocaine-regulated genes in the nucleus accumbens (NAcc) of non-human primates (Macaca fascicularis; cynomolgus macaque), treated daily with escalating doses of cocaine over one year. Changes seen in mRNA levels by hybridization array analysis were confirmed at the level of protein (via specific immunoblots). Significantly up-regulated genes included: protein kinase A alpha catalytic subunit (PKA(calpha)); cell adhesion tyrosine kinase beta (PYK2); mitogen activated protein kinase kinase 1 (MEK1); and beta-catenin. While some of these changes exist in previously described cocaine-responsive models, others are novel to any model of cocaine use. All of these adaptive responses coexist within a signaling scheme that could account for known inductions of genes(e.g. fos and jun proteins, and cyclic AMP response element binding protein) previously shown to be relevant to cocaine's behavioral actions. The complete data set from this experiment has been posted to the newly created Drug and Alcohol Abuse Array Data Consortium (http://www.arraydata.org) for mining by the general research community.

Animals↗

PubMed2000

Predictors of social status in cynomolgus monkeys (Macaca fascicularis) after group formation.

The purpose of the present study was to determine whether various behavioral and hormonal markers obtained in individually housed monkeys would be predictive of social rank following group housing. Body weight, serum cortisol and testosterone levels, and locomotor activity in an open-field apparatus were examined in 20 experimentally naive male cynomolgus monkeys (Macaca fascicularis) while they were individually housed. It was hypothesized that eventual subordinate monkeys would have higher cortisol levels and increased locomotor activity scores. These monkeys were then placed in social groups of four (five pens of four monkeys), and social rank was determined based on outcomes of dyadic agonistic encounters. Body weight correlated significantly with eventual social rank. In general, the heavier the monkey the higher the social rank. Locomotor activity in an open-field apparatus following administration of a low dose of cocaine (0.01 mg/kg, i.v.), which has been shown to increase CNS dopamine, correlated with eventual social rank such that individually housed monkeys with high levels of locomotion were more likely to become subordinate. Serum cortisol and testosterone levels failed to correlate with eventual social rank. Hypothalamic-pituitary feedback sensitivity and adrenal responsiveness were examined by measuring cortisol levels after administration of dexamethasone and following ACTH challenge. Cortisol responses in these tests were not associated with eventual social rank. These results suggest that, in addition to body weight, the level of reactivity in a novel environment after administration of a low dose of cocaine is a potential trait marker for social rank. This trait is apparently not associated with hormone levels, but may involve other CNS mechanisms.

Animals↗

PubMed1998

Further evaluation of the reinforcing effects of the novel cocaine analog 2beta-propanoyl-3beta-(4-tolyl)-tropane (PTT) in rhesus monkeys.

2Beta-propanoyl-3beta-(4-tolyl)-tropane (PTT) is a cocaine analog which has been shown in rhesus monkeys to have cocaine-like discriminative stimulus effects and a long duration of action (>8 h), yet does not function as a reinforcer when substituted for cocaine in monkeys responding under a fixed-interval 5-min schedule (Nader et al. 1997). The purpose of the present study was to evaluate the reinforcing effects of PTT under a fixed-ratio (FR) schedule and to determine if decreasing the inter-injection interval would influence the reinforcing effects of PTT. Male rhesus monkeys (n=3) were trained to respond under a multiple FR 30 food-drug-food schedule. When responding was stable, cocaine (0.003-0.3 mg/kg per injection) or PTT (0.001-0.03 mg/kg per injection) was available during the drug component for at least five consecutive sessions and until stable responding was observed. To investigate whether the inter-injection interval would influence PTT-maintained response rates, the time-out (TO) following PTT injections was reduced from 180 or 300 s to 10 s for at least five consecutive sessions. Cocaine-maintained response rates were characterized as an inverted-U shaped function of dose, with peak rates maintained by 0.03 mg/kg per injection cocaine. PTT (0.001-0.03 mg/kg per injection) maintained response rates significantly higher than rates maintained by the PTT vehicle, but significantly lower than cocaine-maintained response rates; PTT intake increased with a dose. A reduction of the TO following PTT injections to 10 s did not alter PTT-maintained response rates or total session intake. Self-administered PTT was more potent than cocaine at decreasing food-maintained responding. These results suggest that for long-acting compounds like PTT, reinforcing effects are more likely to be observed when the drug is available under a ratio-based schedule, compared to an interval-based schedule.

Animals↗

PubMedDate not supplied

Three-dimensional human pattern visual evoked potentials. I. Normal subjects.

Pattern visual evoked potentials (PVEPs) were obtained from 30 normal adult volunteers, recording from both a conventional horizontal occipital array and three orthogonal bipolar antipodal channels approximating the three dimensions of space. Central and eccentric fixation of 60' checks and central fixation of 30' checks under binocular and monocular viewing conditions was employed. The three antipodal wave forms were displayed as a single 3-D Lissajous trajectory which contained four apices, corresponding to P40 (apex A), N70 (apex B), P100 (apex C) and N125 (apex D). The 3-D evoked potentials depicted the dynamic nature of the human PVEP in terms of changes in the 3-D voltage-voltage-voltage plots of the recordings. The orientation of the A-B, B-C and C-D curvilinear segments reflected the stimulating condition (central fixation vs. right vs. left hemi-field stimulation) for all subjects with more accuracy than did the wave forms from the conventional array. Spherical statistical methods are described for quantifying and evaluating 3-D evoked potential recordings.

Adult↗

PubMedDate not supplied

Three-dimensional human pattern visual evoked potentials. II. Multiple sclerosis patients.

Pattern visual evoked potentials were obtained from 46 patients with definite relapsing/remitting multiple sclerosis, using both a conventional 5-channel occipital array and a 3-D recording technique consisting of three bipolar derivations approximating the three dimensions of space. These three orthogonal wave forms were displayed as a 3-D Lissajous trajectory for each subject. Two of the 15 patients with completely normal conventional pattern VEPs had abnormalities of the orientation of the B-C curvilinear segment of the 3-D pattern VEPs. Delays in the first major occipital positive component (P100) were evident using both techniques; the correlation between P100 latency and the latency of the corresponding trajectory apex was r = 0.99 (P less than 0.01). Post-chiasmal MRI abnormalities were associated with 3-D VEP orientation abnormalities. Three-dimensional pattern VEPs are moderately more sensitive than conventional pattern VEPs at detecting dysfunction posterior to the optic chiasm in demyelinating disease and do not require the use of eccentric fixation to do so.

Adult↗