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Biomedical subjects

M D Schechter

Publications and source records attributed to M D Schechter.

At least 127 records · Page 7Linked to original sources
PubMed1983

Discriminative stimulus control with imipramine: transfer to other anti-depressants.

Discriminative stimulus control with the tricyclic anti-depressant imipramine was attempted in three groups of rats; two of which were subjected to artificially stressful conditions. Only the unstressed group were shown capable of discriminating between the stimulus properties of intraperitoneal 10 mg/kg imipramine and saline in a two-lever, food-motivated operant task. Discriminative performance with decreasing doses of imipramine was shown to be dose-responsive. The ability to discriminate the interoceptive cue produced by imipramine was observed to transfer to a 10 mg/kg dose of both amitriptyline and desmethylimipramine. The results suggest a common tricyclic anti-depressant cueing property.

Amitriptyline↗
PubMed1983

Phenytoin: similarity to tricyclic antidepressants.

Rats were trained to discriminate between the stimulus properties of intraperitoneal injections of 10 mg/kg phenytoin and its pH-adjusted vehicle in a two-lever, food-motivated operant task. Once trained, rats showed a dose-related decrease in discriminative performance with lower phenytoin doses. Administration of pentobarbital and chlordiazepoxide produced vehicle-appropriate responding, whereas injection of imipramine and amitriptyline produced intermediate results. Desipramine, at an intraperitoneal dose of 10 mg/kg, produced a pattern of responding similar to that observed after the training dose of phenytoin. These results demonstrate, for the first time, the ability of a non-disruptive dose of phenytoin to act as a behavioral discriminative stimulus in the rat and suggest the possibility of a common interoceptive cue property with tricyclic antidepressants.

Amitriptyline↗
PubMed1983

The development of brain biogenic amines, cyclic nucleotides and hyperactivity in 6-OHDA-treated rat pups.

Developmental changes in the behavior and brain biochemistry of rat pups were investigated in rats administered intracisternal injections of 6-hydroxydopamine (6-OHDA) or its vehicle at 5 days of age. Although pups of both groups were equivalent in their activity at 15 days of age, 6-OHDA-induced hyperactivity emerged at 20 and 30 days of age in a between-group design in which rats were only tested at one age. Body weight measurements revealed that 6-OHDA-treated rats were underweight at 15, 25 and 30 days of age. Furthermore, at 20 days of age, total activity was inversely related to body weights in the 6-OHDA-treated pups. Whole-brain levels of dopamine (DA) were decreased at every age by the 6-OHDA treatment, whereas norepinephrine (NE) levels were virtually unaffected by 6-OHDA at these same ages. Total activity was inversely correlated with whole-brain DA levels at 20 and 30 days of age when 6-OHDA-treated pups were hyperactive. Measures of cerebellar and "rest-of-brain" adenosine 3',5'-monophosphate (cyclic AMP) and guanosine 3',5'-monophosphate (cyclic GMP) were not uniformly altered by either the 6-OHDA treatment or by maturation. Results are discussed both in terms of brain biochemistry modulation of hyperactivity and the contribution of decreased body weights induced by 6-OHDA to the production of hyperactivity.

Aging↗
PubMed1983

Drug sensitivity of individual rats determines degree of drug discrimination.

Rats were observed to learn to discriminate between the stimulus properties of intraperitoneal 0.16 mg/kg apomorphine and saline, in a two-lever operant task, at different rates. Half of the 12 rats reached criterion performance in a mean of 22.5 session, whereas the other half reached criterion in a mean of 44.2 sessions. These two groups, i.e., the early and later learners, were tested with a range of apomorphine doses and the former group had an ED50 of 0.01 mg/kg, whereas the later group generated an ED50 of 0.07 mg/kg apomorphine. These results suggest that the early learners were significantly more sensitive to apomorphine than the later learners and this may explain the discrepancies in the drug-discrimination literature regarding different ED50's generated at the same drug training dose.

Animals↗
PubMed1983

Open-field behavior in dopamine-depleted rat pups and their mothers.

Possible changes in the behavior of rat mothers and their pups were investigated by administering intracisternal injections of 6-hydroxydopamine (6-OHDA) or its vehicle to 5-day-old rats. Administration of the neurotoxin resulted in a significant depletion of whole-brain dopamine levels to 23% of control levels, whereas norepinephrine levels were reduced to 83% of controls. Open-field behavior revealed that the 6-OHDA-treated rat pups were hypoactive, in terms of decreased square crossings, at 15 days of age, yet were hyperactive at 30 days of age. Toxin-treated pups also showed lower urination scores at 25 and 30 days of age. Mothers' open-field behavior was virtually unaffected by the treatment status of their offspring (i.e., 6-OHDA vs. vehicle-treated), although several of the mothers' behaviors decreased with repeated measures over days.

Aging↗
PubMed1983

Pre- and postnatal effects of caffeine on brain biogenic amines, cyclic nucleotides and behavior in developing rats.

To examine the perinatal effects of caffeine on pup behavior and brain neurochemistry, rat mothers were exposed to caffeine in a choice situation prenatally, postnatally, at both times or at neither time. Prenatally, caffeine-exposed mothers drank approximately 14 mg/kg/day, an amount ineffective in altering mothers' overall prenatal body weight, although it did reliably decrease birth femur length of offspring. Postnatal pup activity measures revealed that postnatal caffeine exposure depressed activity, with an additional contribution of prenatal caffeine exposure. Those effects occurred at caffeine intake levels (circa 48 mg/kg/day) which minimally affected pup body weight, body length, femur length or eye-opening. Postwithdrawal (35 days of age) biochemical determinations revealed significant postnatal effects of caffeine by depressing cyclic AMP/"whole-brain" and elevating the cyclic GMP/cyclic AMP ratio in cerebellum. Whole-brain levels of dopamine and norepinephrine, however, were not affected by the caffeine treatments. These results suggest that activity profiles may be a more sensitive index of caffeine "toxicity" than other indices of physical development, and that cyclic nucleotides may play at least some role in the hypoactivity-inducing effects of caffeine in developing rats.

Animals↗
PubMed1982

Haloperidol-induced hyperactivity in neonatal rats: effect of lithium and stimulants.

The effect of chronic subcutaneous administration of haloperidol directly into neonatal rats was investigated as a possible model for the hyperkinetic syndrome in human children in terms of its onset, duration and offset of hyperactivity. In addition, the ability of chronically-administered lithium in the diet of nursing mothers to attenuate the haloperidol-induced hyperactivity was investigated. Experiments with acute administration of the clinically-effective stimulants, amphetamine and methylphenidate, to the pups were also conducted to determine the adequacy of this behavioral model vis-a-vis the human condition. The results indicate that, although chronic haloperidol (2.5 mg/kg) produced hyperactivity relative to controls on the 25th day of life, this hyperactive behavior does not return to control levels at 30 days of age. Moreover, neither the stimulants nor lithium attenuates this hyperactivity and, indeed, lithium, by itself, produces increased activity. Thus, chronic haloperidol administered directly into neonatal rat pups produces hyperactivity possibly by the production of dopaminergic supersensitivity, yet this effect does not model the temporal course seen in hyperkinetic humans. In addition, the administration of drugs that are clinically-useful in treating childhood hyperactivity were unable to decrease the hyperactivity produced by haloperidol in neonatal rats. Taken together, these observations cast doubt upon the usefulness of this animal model to mimic the human condition.

Animals↗
PubMed1982

Failure of amphetamine isomers to decrease hyperactivity in developing rats.

Possible amphetamine-induced changes in locomotor activity were investigated in developing rats administered intracisternal injections of 6-hydroxydopamine (6-OHDA) or its vehicle at 5 days of age. Administration of the dopamine neurotoxin resulted in a significant depletion of whole-brain dopamine to 44% of control levels, whereas norepinephrine levels were not significantly reduced. In normal and 6-OHDA-treated pups activity increased from moderately low levels at 15 days of age to moderately high levels at 25 days of age. However, 6-OHDA-treated rats were hyperactive at 20 days of age. At 25 days, activity in both groups was equal and declined to levels typical for adults. Administration of graded doses of d- and l-amphetamine generally increased activity in both groups of rats, with d-amphetamine being more potent than l-amphetamine. Furthermore, no dose of either amphetamine isomer decreased activity in 6-OHDA-treated, hyperactive rats. Hence, no convincing evidence was found for a "paradoxical calming" effect of amphetamine in hyperactive rats, supporting other recent reports. These results suggest that the neonatal DA-depleted rat does not provide an accurate model system for pre-clinical investigation of the human hyperkinetic syndrome.

Aging↗
PubMed1982

Dopaminergic activity of quipazine.

Rats were trained to discriminate between the stimulus properties of intraperitoneal 0.16 mg/kg apomorphine and saline in a two-lever, food-motivated operant task. Administration of 1.0 mg/kg quipazine, a putative serotonin agonist, produced apomorphine-appropriate responding with a maximal effect occurring at 45 min post-injection. Pretreatment with either 2.0 mg/kg methysergide or 0.4 mg/kg haloperidol reduced quipazine-induced responding upon the apomorphine-appropriate lever to levels observed with methysergide or haloperidol administered alone. These results evidence a dopaminergic action for quipazine and suggest that central serotonergic and dopaminergic pathways may interact cooperatively to control behavior.

Animals↗
PubMed1982

Behavioral evidence for different mechanisms of action for ethanol and anxiolytics.

1. Stimulus control was established in rats with 600 mg/kg ethanol and saline by employing a two-lever response choice task and an FR10 schedule of food reinforcement. 2. Once trained, rats were tested with lower doses of ethanol (300-525 mg/kg) and with chlordiazepoxide (1.25-5.0 mg/kg) or diazepam (0.32-1.25 mg/kg). The highest doses of each of these treatments were observed to produce ethanol-like responding and decreasing doses produced dose-related effects upon discriminative performance. 3. The ED50 for ethanol was 300 mg/kg, for chlordiazepoxide, 1.20 mg/kg and for diazepam, 0.55 mg/kg. 4. Graphic representation of the dose-response relationships suggested that these anxiolytics share a common site and/or mechanism of action that differs from that of ethanol.

Animals↗
PubMed1982

Time-course of action of ethanol upon a stimulant-depressant continuum.

Rats were trained to discriminate between the interoceptive cues produced by 6.0 mg/kg pentobarbital and 0.8 mg/kg d-amphetamine, both administered intraperitoneally, using a two-lever drug discrimination task. Once trained, intraperitoneal administration of 200 mg/kg ethanol produced pentobarbital-like lever selection at 5 and 15 min post-injection with a return to random levels at 30, 45 and 60 min post-administration. In contrast, administration of 100 mg/kg ethanol produced a significantly greater number of amphetamine-appropriate lever selections at 15 min post-injection. Time-course experiments using 6.0 mg/kg pentobarbital indicated the production of predominantly pentobarbital lever selection for 60 min with a return to random responding (50% on each of the two levers) at 90 min post-administration. These results indicate that a low dose of ethanol can produce more amphetamine-like subjective cues than a higher dose and this effect is time-dependent. Neurochemical evidence is cited to illustrate the biphasic effect of ethanol as it is seen in animals and man.

Animals↗
PubMed1981

Haloperidol-induced supersensitivity to the discrimination of apomorphine.

Rats were trained to discriminate between the stimulus properties of intraperitoneal 0.16 mg/kg apomorphine and saline in a two-lever, food-motivated operant task. Once trained, the rats were tested with the ED50 of apomorphine (0.02 mg/kg) or saline before and 1-22 days after a ten-day regimen of daily 2.0 mg/kg administrations of haloperidol. Chronic haloperidol treatment produced increased discrimination of, and lever selection perseverance to, the low dose of apomorphine when rats were tested at 12 days after the withdrawal of haloperidol and this increased discrimination returned to pre-haloperidol levels by the sixteenth day. The results suggest the development of supersensitivity by prolonged pharmacologic blockade of central dopaminergic receptors with haloperidol and indicate the peak and duration of this effect.

Animals↗
PubMed1981

Extended schedule transfer of ethanol discrimination.

Stimulus control was established in rats with ethanol (600 mg/kg) and saline by employing a two-lever response choice task and an FR10 schedule of food reinforcement. Subjects were then tested with an extended schedule procedure in which lever selection and its perseverance were measured under the training conditions and after the administration of pentobarbital at doses of 2 to 12 mg/kg. With decreasing doses of pentobarbital, drug-lever selection was observed to decline. The dose at which initial lever selection was evenly distributed between the two levers (ED50) was determined to be 4 mg/kg. However, at this dose the perseverance on the ethanol-appropriate lever was not significantly different than that observed after the training dose of ethanol. In addition, the perseverance of saline-lever selection produced by saline was observed to be greater than that produced by the training dose of ethanol on the ethanol-lever. The advantages inherent in employing the extended schedule performance procedure in transfer experiments are discussed.

Animals↗
PubMed1981

Effect of fenfluramine and nicotine upon a stimulant-depressant continuum.

Rats were rapidly trained to discriminate between 0.8 mg/kg d-amphetamine and 6 mg/kg pentobarbital in a two-lever food-motivated operant task by imposing the drug states from the earliest stage of training. Once trained, rats were administered lower doses of each of the training drugs and both d-amphetamine and pentobarbital were observed to produce dose-responsive effects upon discriminative performance. When graphically represented, the dose-response curves were shown to be parallel suggesting a common site and/or mechanism of action. Administration of fenfluramine (1.5 and 2.25 mg/kg) produced pentobarbital-appropriate responding, whereas the injection of three doses of nicotine (0.1-0.4 mg/kg) resulted in amphetamine-like discriminative responding. Inspection of dose-response curves suggested that fenfluramine produces its pentobarbital-like effects by acting differently than does pentobarbital and, although nicotine produces amphetamine-like effects, it acts by a different mechanism than does amphetamine.

Animals↗
PubMed1981

Rapid acquisition of a two-drug discrimination: time of day effect upon saline state.

Rats were rapidly trained to discriminate between 0.8 mg/kd d-amphetamine and 6 mg/kg pentobarbital in a two-lever food-motivated operant task by imposing the drug states from the earliest stage of training, i.e., at the initiation of shaping to lever-press. Once trained, rats were administered each of the training drugs and were allowed to lever press without reinforcement until 10 responses were made on the lever that was not their first choice lever selection. By employing this extended schedule of responding in extinction, the amphetamine-induced interoceptive cue was observed to produce equivalent perseverance as that produced by pentobarbital. However, the administration of saline, the non-drugged state, produced significantly more pentobarbital-appropriate responding than amphetamine-appropriate responding when tested during the daytime, whereas it produced random responding when tested during the night. The results suggest that the arousal state of the rat, a nocturnal species, may differentially influence saline tests in the daytime and in the night time.

Animals↗
PubMed1980

Lack of effect of choline and narcotic antagonists upon apomorphine discrimination.

Rats were trained to discriminate between the stimulus properties of intraperitoneal 0.16 mg/kg apomorphine and saline in a two-lever, food-motivated operant task. Subjects were then injected with either 79 mg choline chloride, 0.02 mg/kg haloperidol, 10 mg/kg naloxone or 10 mg/kg naltrexone prior to apomorphine or saline discriminative testing. Only haloperidol pretreatment was observed to significantly alter the rats' ability to discriminate apomorphine. The results are discussed in relation to the possible mechanism(s) of action of narcotic antagonist and cholinomimetic drug effects upon dopaminergically mediated behaviors.

Animals↗
PubMed1980

Ability of 3-carboxysalsolinol to produce ethanol-like discrimination in rats.

The purpose of the present study was to investigate the possible generalization to 3-carboxysalsolinol (3C-SAL) in a group of rats trained to discriminate a low dose of ethanol (200 mg/kg IP) from the nondrug condition and in antoher group trained to discriminate 0.16 mg/kg IP apomorphine (AP) from the nondrug condition using a drug discrimination paradigm. In test sessions, ED50 for ethanol was 52.0 mg/kg and ED50 for AP was 0.01 mg/kg. In the ethanol-trained rats, 1.8 mg/kg 3C-SAL produced drug responses. In the AP-trained rats, 200 mg/kg ethanol produced drug responses whereas 1.8 mg/kg 3C-SAL produced only a partial drug response. The results are in harmony with the hypothesis that salsolinol in the central nervous system of the rat may be responsible for the discriminability of ethanol. The possible involvement of dopaminergic systems is discussed.

Animals↗