Cathy A. Grover

Academic Dishonesty: Prevalence, Determinants, Techniques, and Punishments

Data from more than 6,000 students regarding the prevalence, causes, techniques, faculty and institutional responsibility, deterrent measures, and punishment dimensions of academic dishonesty are presented.

Acute tolerance to ethanol inhibition of NMDA-mediated EPSPs in the CA1 region of the rat hippocampus

The time course of ethanol-induced inhibition of NMDA-mediated synaptic activity was studied in brain slices using extracellular electrophysiological techniques in the CA1 region of the hippocampus. Bath application of 60 mM ethanol inhibited NMDA-mediated field excitatory postsynaptic potentials (EPSPs) by at least 45% in 7/11 of the slices tested, with the remaining 4 slices inhibited by 8.7-35%. Most slices inhibited by at least 45% showed a significant reduction in ethanol inhibition over a 15 min ethanol exposure period, suggesting the development of acute tolerance. In a second set of experiments, tolerance to ethanol-induced inhibition of NMDA-mediated EPSPs that developed over time during the first ethanol exposure persisted during a second ethanol exposure. In contrast to ethanol, inhibition of EPSPs by the NMDA antagonist DL-2-amino-5-phosphonopentanoic acid (APV) remained stable during a comparable application of the drug. These results suggest that acute tolerance can develop to ethanol inhibition of NMDA mediated synaptic activity in the hippocampus.

Behavioral antagonism between lead and cadmium.

Adult male rats were exposed to one of four dietary conditions for a period of 60 days. Group Control-Diet received a diet containing no added lead or cadmium, group Lead-Diet received a diet that contained 500 ppm added lead, group Cadmium-Diet received a diet that contained 100 ppm added cadmium, and group Lead-Cadmium-Diet received a diet that contained both 500 ppm added lead and 100 ppm added cadmium. Subsequent to exposure, animals were tested in a Digiscan activity monitor. Animals were then sacrificed and metal concentrations were determined in blood and brain. The results from this experiment showed that lead alone increased movement and vertical activity. Cadmium alone decreased movement and increased rest time. Cotreatment with lead and cadmium failed to produce behavioral differences relative to controls; thus, it seems that the changes in activity caused by one metal are antagonized by the other. Results from the analyses of residues in tissues revealed that blood lead concentrations were lower in the cotreatment condition than the lead along condition. However, brain residue accumulations were not different for these two exposure conditions. There was no evidence that the presence of lead attenuated increases in cadmium residues in blood or brain. Overall, the residue data agree with a central, as contrasted with a peripheral, account of lead/cadmium interaction effects, at least as relates to behavior. Because lead and cadmium were additive with regard to producing decreased body weights, it seems that the toxic effect of these metals is antagonized by cotreatment in some instances, and augmented in others.

Ethanol inhibition of NMDA currents in acutely dissociated medial septum/diagonal band neurons from ethanol dependent rats

The effect of acutely applied ethanol and the impact of chronic ethanol treatment, sufficient to induce tolerance and physical dependence, on N-methyl-D-aspartate (NMDA) receptor function were studied in acutely isolated neurons from the medial septum/diagonal band (MS/DB) of adult rats using whole cell, patch-clamp electrophysiology. There was a small positive correlation for capacitance and current amplitude activated by 100 microM NMDA for all groups. Also, cell membrane capacitance was significantly smaller for Ethanol Dependent (approximately 80-84%) than either Naive or Control cells. Therefore NMDA-activated responses were normalized for capacitance (current density, pA/pF) across all three groups. NMDA-activated (30-1000 microM) responses were significantly larger in cells from Control and Ethanol Dependent rats relative to those from Naives. In addition, estimated maximal responses were significantly larger for Ethanol Dependent cells, compared to either Control or Naive, respectively, while EC50s and slopes were not significantly different. Acute 60 mM ethanol significantly inhibited responses to 100 microM NMDA in all three groups, however, mean ethanol inhibition was 12-25% smaller after ethanol dependence. There was no evidence of acute tolerance to ethanol inhibition for any group, but examination of patterns of inhibition for individual neurons showed a few cells were resistant to ethanol or exhibited progressive loss of ethanol inhibition. These results suggest that NMDA receptor function in acutely isolated MS/DB neurons is increased following in vivo chronic ethanol treatment, and shows resistance to acute ethanol inhibition suggesting NMDA receptor-mediated cellular tolerance.

Lead attenuates the antipunishment effects of ethanol

Adult male rats were exposed to a diet containing no added chemicals, or a diet containing 500 ppm added lead (as lead acetate), for 70 days. On Day 71 (training day), after 24 h of water deprivation, all animals were placed in a test apparatus and permitted to make 220 licks for a 5.5 percent (v/v) sucrose in water solution. On Day 72 (test day), all animals received conditioned punishment training where electric shock was delivered to the tongue following every 20 licks of the sucrose and water solution. Prior to commencing punishment training on Day 72, half the animals for the control diet condition (Group Control-Diet-Saline), and half the animals for the lead diet condition (Group Lead-Diet-Saline), received IP injections of saline. Conversely, the remaining half of the animals (Groups Control-Diet-Ethanol and Lead-Diet-Ethanol) received IP injections of 1.5 g/kg ethanol. The results of the conditioned punishment test revealed that animals exposed to a control diet and administered ethanol (Group Control-Diet-Ethanol) engaged in more punished licking and received more shocks than their lead-treated counterparts (Group Lead-Diet-Ethanol). Both of the groups exhibited more punished licking and received more shocks than either of the groups that received saline injections. The possibility that lead contamination may reduce the pharmacologic impact of ethanol is noted.

Effects of Chronic Lead Exposure on Cocaine-induced Disturbance of Fixed-interval Behavior

Chronic lead exposure has been shown to attenuate cocaine-induced increases in extracellular dopamine levels in the region of the nucleus accumbens, and antagonize the locomotor stimulating effects of the drug. The purpose of this study was to determine if similar lead-induced disturbances in the effects of cocaine include the impact of the drug on schedule-controlled responding. Adult male rats exposed ad libitum to water containing 500 ppm lead acetate (Group Lead), or a comparable concentration of sodium acetate (Group Control), were placed on a restricted diet (12-15 g food/day) prior to commencing fixed-interval (F1-5 min) schedule training on Day 33 of exposure. After 27 days of operant training, animals received a sequence of no injection, saline injection, and cocaine injection tests, repeating the sequence for 3, 10, 20 and 40 mg/kg cocaine HCl (i.p.). Local rates were determined for successive 30 s segments of the interval and the pattern of responding was compared under conditions of saline and cocaine injection. For both groups, cocaine increased responding, especially early in the interval. However, the rate enhancing effects of cocaine were less pronounced in lead-exposed animals than controls, at least at the 20 mg/kg dose. These data extend earlier findings and accent the need to examine further the interactive relations between the external chemical environment and drug sensitivity.

Chronic exposure to lead attenuates cocaine-induced behavioral activation

Adult, male rats were exposed to a diet containing 500 ppm (0.05%) lead for 105 days before testing for cocaine-related changes in activity using a Digiscan activity system. Behavioral testing occurred on 6 successive test days. Activity was recorded for 20 min prior to and 40 min after IP injections of either 10, 20, or 40 mg/kg cocaine HCl, with saline injections on the day preceding each drug test day. Cocaine-induced behavioral activation was evident in control diet animals for all three doses (10, 20, and 40 mg/kg). While 10 mg/kg cocaine HCl did not produce behavioral activation in lead-treated animals, both 20 and 40 mg/kg did result in increased activity comparable to that observed in control counterparts.

Lead/ethanol interactions II: Pharmacokinetics

Adult male rats were exposed ad libitum to water containing either 500 ppm lead acetate (group-lead) or an equivalent amount of sodium acetate (group-control) for 60 days prior to receiving ip injections of either 1.0, 2.0, or 3.0 g/kg ethanol (20% v/v). Blood alcohol concentrations (BACs) were recorded over a 6-h time period postinjection, and the groups were compared at each dose for differences in the pattern of ethanol pharmacokinetics. While there was a dose-related effect obtained with increasing ethanol doses producing increasing BAC values, at no dose was there any evidence of group separation at any point during the 6-h postinjection period. These data are instructive with respect to understanding the nature of previously demonstrated lead/ethanol interactions, and rule out the possibility that lead-induced disturbances in the catalysis of ethanol, or some other pharmacokinetic operation, is the basis for the effects of lead on ethanol intake and ethanol administration. Alternative possible accounts of this curious interaction between a xenobiotic contaminant and alcohol are discussed.

Lanthanum and zinc sensitivity of GABAA-activated currents in adult medial septum/diagonal band neurons from ethanol dependent rats

The impact of chronic ethanol treatment, sufficient to induce tolerance and physical dependence, on GABAA receptor function was studied in acutely isolated neurons from the medial septum/nucleus diagonal band (MS/nDB) of adult rats using whole cell, patch-clamp recordings. In ethanol-naive Controls, GABA (0.3-300 microM) induced concentration-dependent increases in Cl- current with a threshold of 0.3-1 microM, a mean maximal current of 7645 +/- 2148 pA at 100-300 microM, an EC50 of 11.3 +/- 1.3 microM and a slope of 1.53 +/- 0.07. GABA-activated currents in neurons from animals receiving two weeks of ethanol liquid diet treatment did not differ significantly on any of these measures. The rate of GABAA receptor desensitization (t1/2 = 6.49 +/- 1.19 s) estimated as the time required for loss of 50% of peak current during sustained application of 10 microM GABA, as well as the residual steady state current remaining following complete desensitization for controls was unchanged by chronic ethanol. The impact of chronic ethanol treatment on the GABAA receptor modulation by lanthanum and zinc which act as positive and negative allosteric modulators, respectively, was also evaluated. Test pulses of 3 microM GABA in control neurons showed maximal potentiation by 141 +/- 30% at approximately 1000 microM lanthanum with an EC50 of 107 +/- 34 microM and a slope of approximately 1. Lanthanum potentiation remained the same following chronic ethanol treatment. Initial estimates based on fitted concentration response curves suggested that maximal inhibition of 3 microM GABA responses by zinc at the level of 70.2 +/- 8.5% in control cells was significantly increased by chronic ethanol treatment to 95.3 +/- 2.5%, although the IC50 of 60.2 +/- 25 microM was not changed. However, this difference was not supported by direct tests of maximal 3-10 mM zinc concentrations. These results suggest that chronic ethanol treatment, sufficient to induce tolerance and physical dependence, probably does not lead to readily detectible changes in GABAA receptor function in MS/nDB neurons.

Lead/ethanol interactions. I: Rate-depressant effects

Adult male rats were exposed to a diet containing 500 ppm added lead as lead acetate (group lead-diet) or a control diet containing no added chemicals (group control-diet) for 61 days prior to commencing fixed-ratio 32 (FR 32) lever press training for water reinforcement. After steady state responding was achieved, all animals received serial administrations of acute doses of ethanol prior to the daily training session. Specifically, lead-diet and control-diet rats received i.p. injections of .25, .5, .75, 1.0, and 1.25 g/kg ethanol, in ascending order, alternating daily with injections of saline. The results revealed a dose-dependent rate-depressant effect, with higher doses of ethanol producing more behavioral suppression than lower doses for both groups. In addition, at the dose of 1.0 g/kg it was observed that the suppressive effects of ethanol on schedule-controlled responding were reduced among lead-treated animals relative to controls. These data are discussed in terms of lead-induced attenuation of the pharmacologic effects of ethanol.