Enhancement of effects of dopaminergic agonists on neuronal activity in the caudate-putamen of the rat following long-term d-amphetamine administration

Amphetamine- and apomorphine-induced changes in the activity of neurons in the caudate-putamen of paralyzed, locally anesthetized rats were recorded in animals pretreated with 2.5 mg/kg d-amphetamine sulphate for 6, 18 or 36 days, or in animals pretreated with saline for 36 consecutive days. In saline-pretreated animals, 2.5 mg/kg d-amphetamine sulphate (IP) produced an initial, brief potentiation of neuronal firing that was followed by a marked depression of neuronal activity lasting for approximately 35 to 110 min after injection. In amphetamine-pretreated animals, this depression of neuronal activity to the same dose of the drug was markedly prolonged, especially in animals given 36 consecutive days of d-amphetamine pretreatment. A similar enhancement occurred in response to 0.25 mg/kg apomorphine (IP) in animals pretreated with amphetamine for 36 days compared to saline-pretreated control animals. These results are discussed in relation to the known behavioral and biochemical effects of acute and long-term amphetamine administration.     

Selective absorption of radio frequency energy due to collective motion of charged domains: case of lysozyme crystal

The role of the N-methyl-D-aspartate (NMDA) receptors in cocaine conditioning and sensitization of locomotor activity was studied in four groups of Sprague-Dawley rats. A sub-motoric dose of the NMDA antagonist MK-801 (0.1 mg/kg, i.p.) was employed using a novel dual-compartment Pavlovian drug conditioning paradigm. The animals were placed sequentially in two different test environments in which locomotor activity was monitored. In the first compartment, the animals always received a non-drug test for 20 min. Upon completion of this test, the animals received either saline, cocaine (10 mg/kg i.p.), MK-801 or MK-801 plus cocaine depending on group assignment and were then placed immediately into the second compartment and again tested for 20 min. A total of six non-drug and six drug tests were conducted every other day over a 12-day period. Across all drug/saline treatment and post-treatment tests for conditioning, there were no statistical differences in locomotor activity among the saline and drug treatment groups in the non-drug test environment. In the drug/saline associated environment, however, cocaine had a reliable stimulant effect on locomotion when administered alone or in combination with MK-801. Following a 1-day and again after 21-days of withdrawal, all animals were administered a non-drug test for conditioning in which no injections were administered. On both tests, all groups had equivalent activity levels in the non-drug environment. In the drug/saline environment, only the cocaine group of the three drug treatment groups exhibited conditioned hyperlocomotion. Importantly, MK-801 blocked conditioned hyperlocomotion in the combined cocaine+MK-801 group. MK-801 did not alter serum or brain cocaine concentration or the cocaine effects on dopamine metabolism in limbic brain tissue. The co-administration of MK-801 with cocaine, however, blocked the corticosterone release effect of cocaine. Thus, the NMDA receptor site appears critical for cocaine induced conditioning and for corticosterone release.     

Effects of the kappa-opioid dynorphin A(1-13) on learning and memory in mice

The effects of intracerebroventricular administration of dynorphin A(1-13) on scopolamine- and pirenzepine-induced amnesia were investigated in mice by observing the step-down-type passive avoidance response and spontaneous alternation performance. The pre- or post-training, or preretention administration of dynorphin A(1-13) (0.3-10 micrograms) alone failed to affect the passive avoidance response, while scopolamine (1 mg/kg) significantly inhibited it. Dynorphin A(1-13) (1 microgram) given 15 min before training and retention tests, but not immediately after training, significantly improved the scopolamine (1 mg/kg)-induced impairment of passive avoidance response, indicating the anti-amnesic effects of dynorphin A(1-13). A lower dose (1 mg/kg) of the kappa-opioid receptor antagonist (-)-(1R,5R,9R)-5,9-diethyl-2-(3-furyl-methyl)-2'-hydroxy-6,7-benzomorpha n reversed the anti-amnesic effects of dynorphin A(1-13) (1 microgram). In contrast, although dynorphin A(1-13) (1, 3 and 10 micrograms) did not influence spontaneous alternation performance, scopolamine (1 mg/kg) and the muscarinic M1 receptor antagonist pirenzepine (3 micrograms) markedly decreased spontaneous alternation performance. Dynorphin A(1-13) (3, 5.6 and/or 10 micrograms) significantly improved the scopolamine (1 mg/kg)- and pirenzepine (3 micrograms)-induced impairment of spontaneous alternation performance. The improving effects of dynorphin A(1-13) (3 micrograms) were almost completely reversed by pretreatment with nor-binaltorphimine (4 micrograms), a kappa-selective opioid receptor antagonist. These results suggest that the stimulation of kappa-opioid receptors improves memory dysfunctions resulting from the blockade of muscarinic M1 receptors.     

The results of inferior and middle meatal antrostomy under endoscopic control

This study examined the extent to which chronic d-amphetamine administration sensitizes animals to some behavioral and neurochemical effects of foot shock stress. Rats received daily injections of saline for 14 days or d-amphetamine (2 mg/kg 7 days and 4 mg/kg 7 days). After a 7 day drug abstinent period, extracellular dopamine, 3,4-dihydroxyphenylacetic acid and homovanillic acid concentrations were measured in the medial prefrontal cortex using in vivo microdialysis in freely moving rats. The behavioral responses to mild foot shock stress were enhanced in the d-amphetamine-pretreated subjects. Concomitant with this behavioral sensitization, d-amphetamine-pretreated subjects showed greater stress-induced increases in extracellular dopamine in the medial prefrontal cortex than in controls. d-Amphetamine (2 mg/kg)-induced stereotyped behavior was also enhanced in the amphetamine-pretreated animals compared to controls; however, d-amphetamine-induced increases in extracellular dopamine in the medial prefrontal cortex were not enhanced in the amphetamine-pretreated group. These results suggest that the mesocortical dopaminergic system is involved in cross-sensitization between d-amphetamine and stress, but not in d-amphetamine-induced behavioral sensitization.     

Tolerance to discriminative stimulus effects of d-amphetamine.

Chronic administration of high doses of d-amphetamine produced time-limited, surmountable tolerance to stimulus effects of d-amphetamine. 23 male Sprague-Dawley rats discriminated saline and 0.80 mg/kg d-amphetamine under fixed ratio (FR) schedules of food delivery. Suspending training and administering saline did not alter sensitivity to d-amphetamine, indicating that neither tolerance nor sensitization developed during regular training. Acute pretreatment with 3.2 mg/kg d-amphetamine did not alter the ED50 for stimulus effects of d-amphetamine. In contrast, administration of 3.2 or 6.4 mg/kg d-amphetamine, b.i.d., for 3 days or 2 weeks increased the ED50 for stimulus effects 3- to 4-fold but did not produce consistent tolerance to rate-altering effects. Tolerance to stimulus effects was surmountable, as higher doses of d-amphetamine produced full drug-lever selection in tolerant rats. Sensitivity recovered after chronic administration ended. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Estrogen improves performance of reinforced T-maze alternation and prevents the amnestic effects of scopolamine administered systemically or intrahippocampally

In a previous study, administration of high doses of estradiol benzoate (100 microgram/kg for 3 days im) to ovariectomized Long-Evans rats counteracted impairments of reinforced T-maze alternation induced by systemic administration of scopolamine, a muscarinic receptor blocker. In the current study, daily administration of lower doses of estradiol benzoate (5 microgram/kg for 3 weeks sc) increased the number of correct reinforced alternations during T-maze acquisition in ovariectomized rats compared to oil-treated controls and prevented impairments of reinforced alternation induced by injection of scopolamine hydrobromide (0.2 mg/kg ip). Furthermore, scopolamine (20 microgram) delivered bilaterally to the dorsal hippocampus reduced reinforced T-maze alternation in ovariectomized rats previously trained to complete this task while daily treatment with estradiol benzoate (5 microgram/kg sc) for 1 week prior to scopolamine infusion counteracted this impairment. In summary, physiological levels of estrogen improved performance during acquisition of reinforced T-maze alternation and prevented impairments induced by scopolamine administered systemically or intrahippocampally.     

Identification of a common mutation (R245H) in Sanfilippo A patients from The Netherlands

Two groups of male rats were tested to determine whether pre-exposure to d-amphetamine would enhance the motivation to self-administer the drug under a progressive ratio schedule of reinforcement. In the first phase of the experiment, one group of rats received d-amphetamine (2 mg/kg IP), while a second group received saline on alternate days for a total of ten injections. Following a 21-day drug withdrawal period, behavioral sensitization was confirmed by a significant increase in amphetamine-induced stereotypy in the d-amphetamine-pretreated group, relative to the saline-pretreated group. In the second phase of the study, all rats were implanted with chronic jugular catheters and trained to self-administer d-amphetamine (0.2 mg/kg per infusion) under a fixed-ratio schedule of reinforcement. The progressive ratio paradigm was then imposed for 7 consecutive days; d-amphetamine-pretreated rats attained significantly higher break points than saline-pretreated animals. These data suggest that pre-exposure to d-amphetamine may enhance the motivation to self-administer this drug.     

The "worth" of routine spirometry in a cystic fibrosis clinic

The effects of Rivastigmine, a novel centrally-acting anticholinesterase agent, were evaluated on cerebral edema, neurological and motor deficits, and impairment of spatial memory induced in mice by closed-head injury (CHI). Severe injury was induced in the left hemisphere of mice under ether anesthesia. Rivastigmine (1 or 2 mg/kg) or saline (10 ml/kg) was injected SC 5 min later. Rivastigmine (2 mg/kg) reduced cerebral edema by at least 50% (p < 0.01), 24 h after CHI and accelerated the recovery of motor function 7 and 14 days after CHI. Control mice (n = 24), previously trained to find the goal platform in a Morris water maze failed to recall or relearn its position for at least 11 days post-injury. Those given a single injection of Rivastigmine (2 mg/kg) regained their pre-test latencies by the third day after CHI. The neuroprotective effects of Rivastigmine on brain edema, neurological and motor function, and performance in the Morris water maze were completely antagonized by simultaneous SC injection of either scopolamine (0.5 mg/kg) or mecamylamine (2.5 mg/kg). The antagonists alone had no significant effect on any of these parameters. These data show that the reduction by Rivastigmine of the immediate and long-term sequelae of brain injury are mediated by increased cholinergic activity at both muscarinic and nicotinic receptors.     

Recurrent electromechanical dissociation due to severe underlying coronary heart disease

The "thermoregulatory theory of hunger" posits that rats placed in a cold environment should increase the amount of food intake, while rats placed in a hot environment should decrease their food intake. d-Amphetamine causes hyperthermia among rats kept at warm ambient temperature, and results in hypothermia among animals kept in a cold environment. d-Amphetamine-caused-hyperthermia should therefore result in decreased eating behavior, and d-amphetamine-caused hypothermia should result in increased eating behavior. One must take into account the fact that d-amphetamine is an anorexic drug. The interaction between (a) ambient temperature, (b) body temperature and (c) food intake were tested on groups of rats injected with various doses of d-amphetamine (1.5-15 mg/kg) and placed in ambient temperatures ranging from 4-37 degrees C. No increase in food intake was revealed under any dosage or temperature condition. The decrease in food intake found with d-amphetamine treated animals could not be explained in the "thermoregulatory theory of hunger". Our data indicate that d-amphetamine anorexic effects and thermal effects are mediated by different mechanisms.     

Protein kinase C isotypes theta, delta and eta in human lymphocytes: differential responses to signalling through the T-cell receptor and phorbol esters

CD-1 mice received daily subcutaneous injections of either cocaine (20 mg/kg or 40 mg/kg) or saline solution (0.9% NaCl) from postnatal days 2 to 15. Pups were tested on days 16-17 for learning and 24-h retention of a passive avoidance task, where entering a dark compartment was punished with a mild foot shock. Locomotor activity and general behaviour in an open field arena were assessed on day 21, following administration of either the muscarinic blocker scopolamine (0.8 mg/kg) or saline solution. In addition, immunostaining for the enzyme choline acetyltransferase (ChAT) was measured in different basal forebrain areas (medial septum, striatum, and nucleus basalis) on day 30. Cocaine treatment failed to affect either learning or retention capabilities. Nonetheless, neophobic behaviour during the learning session was enhanced in control nonpunished mice exposed to the 20-mg/kg dose. In the open field test, although baseline activity levels were unaffected by cocaine exposure, the 40-mg/kg cocaine-treated pups showed decreased sensitivity to the hyperkinetic effects of scopolamine. ChAT immunocytochemistry revealed a significant reduction of the number of ChAT-immunopositive neurons in the nucleus basalis but not in the other cholinergic basal forebrain regions.     

Regulatory effect of danggui-shaoyao-san on central cholinergic nervous system dysfunction in mice

Since administration of a powdered extract (TSS) of Danggui-Shaoyao-San (Toki-shakuyaku-san in Japanese) alone to naive mice had no influence on ACh levels in the brain, the present study examined the effect of TSS on the central cholinergic nervous system using mice treated with scopolamine (0.5 mg/kg) or mecamylamine (0.05 mg/kg), which affects the cholinergic nervous system. TSS was suspended in a 5% carboxymethylcellulose solution and mice were orally given single or repeated (twice a day, for 14 days) administration of TSS at 50 or 500 mg/kg. Results on spontaneous locomotor activity showed that (1) single administration of TSS at 50 or 500 mg/kg to naive mice significantly inhibited vertical and horizontal locomotor activities, while repeated administration of TSS at 50 mg/kg significantly stimulated both activities; (2) in mice treated with scopolamine, repeated administration of TSS at 500 mg/kg significantly inhibited the scopolamine-induced increase in locomotor activities, whereas in mice treated with mecamylamine, single or repeated administration of TSS at 50 and 500 mg/kg did not show any influence on the mecamylamine-induced decrease in locomotor activities. Regarding the step-down passive avoidance responses; single administration, but not repeated administration, of TSS at 50 and 500 mg/kg significantly inhibited scopolamine-induced shortening of step-down latency. In mice treated with mecamylamine, TSS did not exert any influence on the step-down latency. As for ACh contents, single or repeated administration of TSS at 50 or 500 mg/kg to naive mice had no influence on the levels of ACh in the cerebral cortex, corpus striatum or hippocampus. However, the levels of brain ACh in mice treated with scopolamine showed a decrease and a single administration of TSS at 500 mg/kg significantly inhibited this scopolamine-induced decrease in ACh levels. These results indicate that TSS ameliorates dysfunction of the central cholinergic nervous system and scopolamine-induced decrease in ACh levels in mouse brain, but has no influence on ACh levels in naive mice. Thus, it suggests that TSS may be a useful therapeutic agent in Alzheimer's disease and senile dementia.     

Uncertainty analysis for wheelchair propulsion dynamics

Nefiracetam is undergoing preclinical and clinical tests as a cognition-enhancing drug in Alzheimer's disease (AD). Nicotinic cholinergic receptors are lost in AD, and nicotinic as well as muscarinic cholinergic receptors are involved in the modulation of eyeblink conditioning. Experiments were carried out using young rabbits to examine the effect of nefiracetam on cholinergic antagonists to nicotinic (mecamylamine) and muscarinic (scopolamine) receptors. Rabbits were tested for 15 days in the 750 ms delay eyeblink classical conditioning paradigm in paired and explicitly unpaired conditions. Nefiracetam at a dose of 15 mg/kg significantly ameliorated the effects of 0.5 mg/kg mecamylamine, and nefiracetam at a dose of 10 mg/kg significantly ameliorated the effect of 1.5 mg/kg scopolamine. The vehicle alone and nefiracetam alone groups performed similarly to the groups treated with mecamylamine or scopolamine and nefiracetam. Reversal by nefiracetam of a nicotinic as well as a muscarinic cholinergic antagonist indicates that the drug may affect deficits specific to AD.     

Reinforcement magnitude modulation of rate dependent effects in pigeons and rats.

Response rate can influence the behavioral effects of many drugs. Reinforcement magnitude may also influence drug effects. Further, reinforcement magnitude can influence rate-dependent effects. For example, in an earlier report, we showed that rate-dependent effects of two antidepressants depended on reinforcement magnitude. The ability of reinforcement magnitude to interact with rate-dependency has not been well characterized. It is not known whether our previous results are specific to antidepressants or generalize to other drug classes. Here, we further examine rate-magnitude interactions by studying effects of two stimulants (d-amphetamine [0.32–5.6 mg/kg] and cocaine [0.32–10 mg/kg]) and two sedatives (chlordiazepoxide [1.78–32 mg/kg] and pentobarbital [1.0–17.8 mg/kg]) in pigeons responding under a 3-component multiple fixed-interval (FI) 300-s schedule maintained by 2-, 4-, or 8-s of food access. We also examine the effects of d-amphetamine [0.32–3.2 mg/kg] and pentobarbital [1.8–10 mg/kg] in rats responding under a similar multiple FI300-s schedule maintained by 2- or 10- food pellet (45 mg) delivery. In pigeons, cocaine and, to a lesser extent, chlordiazepoxide exerted rate-dependent effects that were diminished by increasing durations of food access. The relationship was less apparent for pentobarbital, and not present for d-amphetamine. In rats, rate-dependent effects of pentobarbital and d-amphetamine were not modulated by reinforcement magnitude. In conclusion, some drugs appear to exert rate-dependent effect which are diminished when reinforcement magnitude is relatively high. Subsequent analysis of the rate-dependency data suggest the effects of reinforcement magnitude may be due to a diminution of drug-induced increases in low-rate behavior that occurs early in the fixed-interval. (PsycINFO Database Record (c) 2011 APA, all rights reserved)     

Effects of nicotine on neocortical electrical activity in rats

The present study investigates the effects of acute and repeated nicotine i.p. treatment on cortical EEG activity. Nicotine at 0.3 and 0.9 mg/kg, but not at 0.1 mg/kg, decreased high voltage spindles (HVSs). Nicotine at 2.7 mg/kg suppressed HVSs completely. Mecamylamine, a nicotinic cholinergic antagonist, increased HVSs at 5 and 7.5 mg/kg. Nicotine blocked the HVS induction induced by mecamylamine. Mecamylamine at 1.25 mg/kg antagonized the HVS suppressing action of nicotine at 0.3 mg/kg. The muscarinic cholinergic antagonist, scopolamine (0.2 mg/kg), increased the 1 to 20 Hz amplitude sum value, and this increase was blocked to some extent by the highest dose of nicotine (2.7 mg/kg). However, nicotine did not block the effect of a higher scopolamine (2.0 mg/kg) dose on the sum amplitude values. Mecamylamine at 2.5 and 7.5 mg/kg blocked the effect of nicotine at 2.7 mg/kg on the EEG sum amplitude values in scopolamine (0.2 mg/kg)-treated rats. The peripherally acting nicotinic and muscarinic cholinergic antagonists, hexamethonium and scopolamine methylbromide, had no effect on spectral EEG and HVS values. In quisqualic acid nucleus basalis-lesioned rats, a frontal cortical choline acetyltransferase depletion (-72%) and slowing of the EEG was observed. Nicotine could not restore EEG activity in nucleus basalis-lesioned rats. After repeated (10 days, three injections/day) administration of nicotine, no tolerance to the effects of either nicotine (0.9 mg/kg) on spontaneously occurring HVSs or nicotine (2.7 mg/kg) on the EEG change induced by scopolamine was observed. The present results show that nicotinic receptor stimulation desynchronizes neocortical EEG activity in normal animals, but this action disappears in basal forebrain-lesioned animals. Therefore, it is likely that the effects of nicotine in reversing EEG and behavioral abnormalities observed in Alzheimer's disease may be limited if the basal forebrain cell loss is extensive.     

Behavioral and subjective effects of D-amphetamine and modafinil in healthy adults.

Modafinil is indicated for the management of excessive daytime sleepiness; however, recent studies have examined a broad range of potential uses. Given that clinical uses of modafinil may be expanding, this study compared modafinil and d-amphetamine effects on subjective and performance measures. Across 11 sessions, 11 healthy adults were tested after oral doses of placebo (5 sessions), modafinil (1.75 mg/kg, 3.50 mg/kg, or 7.00 mg/kg), and d-amphetamine (0.035 mg/kg, 0.070 mg/kg, 0.140 mg/kg) under double-blind, randomized conditions. Assessments of cognitive performance and subjective effects were completed before drug administration, 30 min after drug administration, and at hourly intervals after drug administration for 5 hr. Modafinil increased ratings on the Amphetamine and Morphine Benzedrine Group scales of the Addiction Research Center Inventory (ARCI) and increased ratings on the Vigor and Total Positive scales of the Profile of Mood States. d-Amphetamine increased visual analog ratings of feeling stimulated and liking the drug and increased ratings on the Morphine Benzedrine Group scale of the ARCI. Both medications significantly reduced visual analog scale ratings of feeling sleepy, and modafinil decreased ratings on the ARCI Pentobarbital-Chlorpromazine-Alcohol Group scale. Both medications sustained performance that deteriorated across time on the Sternberg Number Recognition Test. Modafinil also enhanced performance rate on the Digit-Symbol Substitution Task above baseline levels and increased response rate on the Repeated Acquisition of Response Sequences Task. These results suggest that modafinil engenders alerting effects and increases performance in healthy non-sleep-deprived individuals comparable with that of d-amphetamine. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Comparison of the effects of morphine, pentazocine, cyclazocine and amphetamine on intracranial self-stimulation in the rat

Rats were trained to press a lever in order to stimulate their hypothalamus through a chronically implanted electrode. Dose-response curves were determined for the effects of morphine (0.3-10 mg/kg), pentazocine (1.0-30 mg/kg), cyclazocine (0.03-30 mg/kg) and d-amphetamine (0.1-3.0 mg/kg) on responding for intracranial stimulation, and then were redetermined in the presence of one or two doses of naloxone. The three analgesics produced only dose-related decreases in responding with the following relative potencies: cyclazocine greater than morphine greater than pentazocine. The well-documented rate-increasing effects of d-amphetamine on intracranial self-stimulation were observed at 0.3 and 1.0 mg/kg of the drug; decreases in responding at 3.0 mg/kg were associated with stereotyped behavior. Naloxone, which had no effect of its own on self-stimulation, increased the dose of the analgesics required to depress response rate in a manner consistent with a competitive antagonism. In contrast, response rates at all doses of d-amphetamine tested in the presence of naloxone. Thus, the interaction between naloxone and d-amphetamine is qualitatively different from the one between naloxone and the analgesics. This finding extends to intracranial self-stimulation the generality of a previous report of interactions between d-amphetamine and naloxone on behavior in the rat.     

Characteristics of target-reaching in cats. III. Lifting and protraction with an obstacle in the movement path and after its removal

We have established a rat model that reflects the course of development of alcohol and opiate addiction. The present study with d-amphetamine aimed to define general principles in the development of an addiction. Male rats had a continuous free choice between d-amphetamine solutions (100, 200 and 400 mg/l) and water for 47 weeks. An initial intake of high doses of d-amphetamine during the first weeks of drug choice was followed by an individually stable pattern of drug consumption of moderate drug doses. During this period of controlled consumption (from week 10 to week 40), the voluntary intake of d-amphetamine depended on individual factors (dominant rats: 0.37+/-0.02 mg/kg per day, subordinate rats: 0.57+/-0.05 mg/kg per day) and environmental variables (group housing: 0.21+/-0.02 mg/kg per day, single housing: 0.41+/-0.03 mg/kg per day). Beginning with week 41, voluntary d-amphetamine consumption progressively increased (1.9+/-0.2 mg/kg per day in week 47), although the experimental conditions remained unchanged. Drug intake during a retest (free choice as before) after 6 months of drug deprivation revealed that the rats had persistently lost their control over drug intake and were no longer able to adjust drug taking to internal and external conditions. These addicted rats took very high drug doses, even when all d-amphetamine solutions but not water were adulterated with bitter tasting quinine (6.6+/-0.6 mg/kg per day; age-matched controls: 0.37+/-0.04 mg/kg per day). Forced intake of d-amphetamine for 47 weeks (7.1+/-0.3 mg/kg per day) via the drinking fluid caused physical dependence (hyperreactivity during withdrawal) but did not lead to drug addiction (voluntary intake in the retest with adulteration: 0.42+/-0.04 mg/kg per day). Both the temporal development and the prerequisites of psychostimulant addiction were in principle the same as for alcohol and opiates.     

RNA virus in Allomyces arbuscula: ultrastructural localization during the life-cycle

Three experiments were concerned with tolerance to anorexia induced by d-amphetamine. In experiment 1, one group of rats on a 2 hr food deprivation schedule received 2 mg/kg of d-amphetamine 15 min before eating every other day for a month. A second group of rats on a similar schedule received the same dose of d-amphetamine immediately after eating. When compared to a saline-treated control group, the former group showed significant decreases in weight and food intake; tolerance to the amphetamine-induced anorexia began to occur toward the end of the experiment. The latter group showed a significant decrease in food intake on the non-drug days and an overall weight loss when compared to the control group. Experiment 2 demonstrated that tolerance to d-amphetamine-anorexia was related to the duration of drug administration per se. Experiment 3 showed that taste can be a factor in influencing the rate of tolerance to d-amphetamine-induced anorexia. These results indicate that both pharmacological and experiential factors play an important role in determining the rate of tolerance to this action of d-amphetamine.     

Immediate and long-term effects of neonatal MK-801 treatment on nonspatial learning

These experiments observed the immediate and long-term effects of neonatal treatment with MK-801 on patterned single alternation (PSA), a form of nonspatial, memory-based learning. Rat pups were injected daily on postnatal days (PND) 7-19, with MK-801 (MK+) or the less active isomer of MK-801 (MK-) (0.25 mg/kg), and trained at either PND 22 or 60. Rats treated with MK+ or MK- and trained on PND 22 were significantly impaired in PSA when compared with the saline control. Beyond the learning impairment, MK+ rats showed an overall decreased running speed during training. They also presented an array of abnormal behaviors and significant weight loss. These nonassociative variables were determined for several doses (0.025, 0. 05, 0.1, 0.15, and 0.20 mg/kg) through PND days 22-25. Rats that received the threshold dose for secondary effects (0.025 mg/kg) also showed an overall decrease in running speed, but failed to show a significant nonspatial learning impairment on PSA. The PSA learning impairment was found to be not long lasting; rats trained at PND 60, after neonatally receiving the original high dose of MK-801, did not differ from controls.     

Doxorubicin, vincristine, and cis-diamminedichloroplatinum (II) therapy in patients with advanced breast cancer

Thirty-six male albino rats were injected with either saline or 0.6 mg/kg scopolamine and placed on a metal grid. The grid was wired to a transistor-biased detector which determined, every second, whether the subject's resistance was above or below a preset threshold value. Over test sessions of five minutes, drug subject's resistances were above each of the three threshold values used (5, 10, 15 megohms) for significantly longer than those of control subjects. Scopolamine treated rats would therefore receive lower shock levels than control subjects in a shock experiment.