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Biomedical subjects

C Kornetsky

Publications and source records attributed to C Kornetsky.

At least 91 records · Page 5Linked to original sources
PubMed1979

Intracranial self-stimulation thresholds: a model for the hedonic effects of drugs of abuse.

We present the thesis that many drugs of abuse are used for their hedonic effects and that a relevant animal model for the study of these effects is the action of these drugs on the pathways that support rewarding intracranial self-stimulation. A relationship between abuse potential of a drug and its ability to lower the threshold for rewarding brain stimulation in the rat was found. Of all the compounds we have studied, morphine and cocaine were the drugs that caused the maximum lowering of the rewarding threshold. Phencyclidine hydrochloride and the mixed agonist-antagonist pentazocine also lowered the threshold to a lesser degree, while the mixed agonist-antagonists cyclazocine and nalorphine hydrochloride had inconsistent effects. Naloxone hydrochloride, at the doses tested, had no effect on the threshold. Further, there is no evidence that tolerance develops to the threshold-lowering effect of morphine, suggesting that continued use of narcotics by the physically dependent individual is not simply due to an effort to avoid the pain of withdrawal.

Animals↗
PubMed1979

Specific modulation of brain stimulation reward by haloperidol.

Low doses of haloperidol (3--18 micrograms/kg) caused dose related increases in reinforcing thresholds for self-stimulation to the medial forebrain bundle in rats. These effects, which were demonstrated completely independent of performance variables, indicate a direct modulation of central reinforcement processes by this drug, at doses which have highly selective action on dopaminergic neurotransmission.

Animals↗
PubMed1979

Euphorigenic drugs: effects on the reward pathways of the brain.

This report summarizes a number of experiments designed to examine the changes in the threshold for intracranial self-stimulation (ICSS) in the rat after the administration of morphine and a number of narcotic agonist-antagonists, as well as three nonnarcotic drugs that have extensive nonmedical use (cocaine, d-amphetamine, and phencyclidine). The results of these experiments clearly indicate that morphine lowers the threshold for ICSS and, furthermore, there appears to be little or no tolerance to this effect. The only mixed agonist-antagonist that consistently lowered the ICSS threshold was pentazocine. Cocaine, d-amphetamine, and to a lesser degree, phencyclidine also lowered the ICSS threshold. These results suggest that the abuse liability of these agents may be directly related to their ability to sensitize the neural substrate involved with natural reward.

Amphetamine↗
PubMed1978

Cocaine: acute effects on reinforcement thresholds for self-stimulation behavior to the medial forebrain bundle.

Reinforcing thresholds for self-stimulation behavior to the medial forebrain bundle were determined in rats by means of rate-free psychophysical method. The acute administration of cocaine lowered the reinforcing thresholds independent of motor stimulatory effects. These results indicate that cocaine affects the sensitivity of the reward pathways in the brain, and further demonstrate the utility of rate-independent methods in the assessment of drug effects on self-stimulation behavior.

Animals↗
PubMed1976

Effects of chronic d-amphetamine on social behavior of the rat: implications for an animal model of paranoid schizophrenia.

Hooded rats in a social colony were given increasing daily doses of d-amphetamine up to 8 mg/kg. Time-lapse 16 mm cinematographically recorded behavior was analyzed for the following: grooming, feeding, sex, sleeping, resting, sterotypy, agonistic behavior, muricidal activity, and the location and movement of each rat. Subordiant rats receiving d-amphetamine actively withdrew from social interactions by retreating to strategically defensible locations in the environment. They remained hypervigilant of other rats and overreacted to their approaches by either fleeing or by defensively rearing and "boxing". On the other hand, when the dominant rat received the maximum dose, it seemed totally oblivious to the other rats. The responses to drug treatment in subordinant rats may provide a model for the social behavior of frightened paranoid schizophrenics.

Animals↗
PubMed1976

Hyporesponsivity of chronic schizophrenic patients to dextroamphetamine.

Among the evidence supporting the dopamine hypothesis of schizophrenia is the finding that both amphetamine and methylphenidate hydrochloride, potent releasers of dopamine, can cause exacerbation of symptoms in the acute schizophrenic patient. The present report describes three experiments in which the effects of amphetamine in chronic schizophrenic patients were studied. In one of the experiments, orally administered, daily doses of 20 mg of dextroamphetamine sulfate given at 8 PM had little or no effect on the sleep duration of the subjects. In the other two experiments, doses up to 40 mg given orally also had little or no effect on the performance of the subjects on a variety of behavioral tests. There was no evidence of an exacerbation of the disease process in any of the subjects. The most consistent amphetamine effect was a dose-related increase in blood pressure. These results indicate that the chronic schizophrenic patient may be hyporesponsive to amphetamine and suggest that if the dopamine hypothesis is correct, then it must be modified to take into account these findings in the chronic patient.

Adult↗
PubMed1976

Naloxone blockade of morphine analgesia: a dose-effect study of duration and magnitude.

The purpose of the experiment was to determine the minimal dose of naloxone needed to block the analgesic effect of morphine as measured by the foot-shock titration procedure in the rat. Various groups of rats received, subcutaneously, various doses of naloxone hydrochloride, from 0.03 to 2.0 mg/kg, 15 minutes before receiving 10 mg/kg of morphine sulfate. The results indicate that 1.0 mg/kg of naloxone is the minimum dose necessary to provide full blockade of the measured morphine effect for up to 5 hours after the morphine administration. Partial blockade was evident at doses much smaller than 1.0 mg/kg of naloxone. A dose of 0.125 mg/kg of naloxone completely blocked the onset of a measurable effect from 10 mg/kg of morphine for 60 minutes in six out of the seven animals tested at that dose. The results provide a clear dose-effect relationship for both magnitude and duration of naloxone blockade of the analgesic effect of morphine.

Animals↗
PubMed1975

Effects of testing age and fostering experience on seizure susceptibility of rats treated prenatally with chlorpromazine.

Offspring of rats treated with 2 mg/kg body weight chlorpromazine (CPZ) on Days 5-8 of gestation had lower seizure thresholds than offspring of saline-treated controls at 30, 60, 90, and 120 days of age. The CPZ-treated offspring were also heavier than controls prior to weaning. Further analysis using cross-fostered litters indicated that at least part of the drug effect on seizure thresholds took place before birth, although a postnatal component was also demonstrated. A striking effect of the fostering experience itself on the seizure threshold prevented conclusions about the relative importance of prenatal and postnatal influences.

Age Factors↗