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J B Appel

Publications and source records attributed to J B Appel.

At least 73 records · Page 4Linked to original sources

d-Amphetamine and fixed-interval performance: effects of establishing the drug as a discriminative stimulus.

The effects of d-amphetamine were examined as a function of conditioning history. The compound (0.5 mg/kg) (1) increased the response rate of rats under a fixed-interval 60-sec schedule, (2) produced greater increases in responding under the fixed-interval schedule when drug administration had been explicitly paired with a fixed-ratio 20 schedule, and (3) decreased responding under the fixed-interval schedule when the drug had been paired with electric shock punishment. Randomly giving amphetamine before fixed-ratio or punishment sessions did not produce such modifications of drug effects under the fixed-interval schedule. These results, like earlier findings, indicate that drug effects can be modified by conditioning history.

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Effects of quipazine on behavior under a multiple schedule of reinforcement.

The effects of three doses of quipazine (1.0, 5.0 and 10.0 mg/kg) on the performance of rats under a multiple fixed-ratio 15 fixed-interval 60-sec schedule of food reinforcement were examined. In the absence of drug, response rates under the fixed-ratio component were much higher than response rates under the fixed-interval component. Rates under the fixed-ratio component were decreased by quipazine in dose-dependent fashion, while response rates under the fixed-interval component were increased by the lowest dose and decreased by the two higher doses of the drug.

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Role of peripheral mechanisms in the behavioral effects of 5-hydroxytryptophan.

The effects of 5-hydroxytryptophan (5-HTP) were studied in rats trained to press a lever under a fixed-ratio (Fr-32) schedule of water presentation. d-, l-and d,l-5-HTP all decreased responding in a dose-related manner. The levo isomer (12.5-25 mg/kg) was twice as potent as the racemic form (25-50 mg/kg) in this respect. Moderate doses of d-5-HTP (less than 100 mg/kg) did not affect responding, whereas 200 mg/kg produced almost complete suppression. The response decrement produced by 25 mg/kg l-5-HTP was completely antagonized by pretreatment with either 50 mg/kg or 400 mg/kg of the decarboxylase inhibitor, benserazide (Ro4-4602). The specific peripheral decarboxylase inhibitor, carbidopa (MK-486) (50 mg/kg) and the peripheral serotonergic antagonist, xylamidine tosylate (1 mg/kg) also antagonized the effects of 25 mg/kg l-5-HTP. These results suggest that at least some of the behavioral effects of 5-HTP are due to increases in levels or turnover of 5-HTP in peripheral serotonergic neuronal systems.

5-Hydroxytryptophan↗

Drug effects under automaintenance and negative automaintenance procedures.

Three food-deprived pigeons were initially exposed to an automaintenance procedure in which brief periods of response key illumination were followed by food delivery without regard to the subject's behavior. Keypecking occurred at a high rate while the key was illuminated and was reduced in dose-dependent fashion by acute administration of LSD (0.05--0.45 mg/kg), quipazine (1.0--8.0 mg/kg), haloperidol (0.08--0.32 mg/kg), and pentobarbital (4.0--16.0 mg/kg). The animals were then exposed to a negative automaintenance procedure in which food delivery followed key illumination only if the lighted key was not contacted. Keypecking occurred at a low rate under this procedure, with no responses occurring during the majority of key illuminations and was decreased or unaffected by LSD, quipazine, and haloperidol; pentobarbital increased responding at doses of 4.0 mg/kg and 8.0 mg/kg and reduced responding at a dose of 16.0 mg/kg.

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Behavioral sensitivity to LSD: dependency upon the pattern of central 5HT depletion.

Two experiments were carried out using a fixed ratio (FR) schedule of water reinforcement to determine the efficacy of two serotonin (5HT) depleting agents (p-chloroamphetamine, 5, 7-dihydroxytryptamine) in altering sensitivity to a low dose of LSD (0.02 MG/KG). The results showed that while both p-chloroamphetamine (PCA) and 5, 7 dihydroxytryptamine (5, 7 DHT) were efficacious in reducing whole brain 5HT, only 5, 7 DHT altered LSD sensitivity such that a 0.02 mg/kg dose of LSD given 12 days after 5, 7 DHT administration disrupted bar press behavior. This was not observed in animals given PCA within similar parameters. Moreover, 4 animals given PCA that did not show increased sensitivity to LSD, did show behavioral disruption to LSD (0.02 mg/kg when they were pretreated with p-chlorophenylalanine, Results are discussed on terms of a possible particular pattern of 5HT depletion that must be achieved before sensitivity to LSD is observed.

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Drug-induced conditioned suppression: specificity due to drug employed as UCS.

The classical conditioning potential of several drugs was tested in rats by pairing a light CS with the drug UCSs; these stimuli were superimposed in a variable-interval 30 sec schedule for water reinforcement. Conditioning (suppression of bar-pressing in the presence of the CS) was definitely demonstrated with psilocybin (2.0 mg/kg), was suggested but not clearly shown with LSD (0.13 MG/kg), and was not evident with methyl atropine nitrate (50 mg/kg) or pentobarbital (25 mg/kg). These results indicate that previously demonstrated drug-induced conditioned suppression is not a nonspecific effect of unconditioned suppression but depends on the type of drug employed.

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Blockade of the behavioral effects of 5-HTP by the decarboxylase inhibitor Ro 4-4602.

Twenty male rats were trained to press a bar on a fixed-ratio (FR 32) schedule of water reinforcement. The behavioral effects of 5-HTP (50 mg/kg) were studied following pretreatment with small (50 mg/kg) and large (400 mg/kg) doses of the decarboxylase inhibitor Ro 4-4602. It was found that both doses of the pretreatment agent blocked the disruptive effects of 5-HTP. This result suggests that at least some of the effects of 5-HTP may be mediated peripherally.

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Alterations in the behavioral effects of LSD by motivational and neurohumoral variables.

Forty naive male albino rats were trained to press a bar on a fixed-ratio (FR 32) schedule of water reinforcement. They were then divided into two groups, one of which (N = 20) received 5 min of extra water 12 hr before each experimental session; the other group (N = 20) received no extra water. Half of the animals in each group was given three daily doses (100 mg/kg) of the trytophan hydroxylase inhibitor p-chlorophenylalanine methyl ester (PCPA) while the remaining animals were given control injections of the PCPA vehicle. Ten days following the last administration of PCPA (or vehicle) all animals were given a low dose of LSD (20 mug/kg). Bar-pressing behavior was significantly disrupted only in those animals receiving both PCPA and extra water. Central (whold brain) concentrations of serotonin (5-HT) were significantly lower in all animals which had been treated with PCPA. These results, along with those previously reported, suggest that amount of deprivation can be an important determinant of both the ability of drugs to alter behavior and the dependence of such alterations upon underlying neuronal activity.

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Stimulus properties of the narcotic antagonist pentazocine: similarity to morphine and antagonism by naloxone.

Pentazocine (10 mg/kg) and saline were used as discriminative stimuli in rats. After pentazocine administration, reinforcement could be obtained contingent on pressing one particular lever (left or right) in a two-lever operant chamber. Responding on the opposite lever was reinforced only after saline injections; a drug-lever combination was always held constant for each animal. Discriminated choice responding between pentazocine and saline was learned to an 80% correct criterion. Test injections of morphine produced dose-related responding on the pentazocine lever. Choice responding after 7.5 mg/kg of morphine was not significantly different from choice responding after 10 mg/kg of pentazocine. The discriminable ED50 values for both pentazocine and morphine were estimated from dose-response curves and when given in combination (pentazocine ED50 + morphine ED50), more drug-related responding occurred than occurred after either drug (ED50) alone. Naloxone produced saline-like responding but antagonized the stimulus properties of both pentazocine and morphine. However, the antagonism of the morphine cue by naloxone was significantly greater than the antagonism of the pentazocine cue. The results indicate that pentazocine and morphine are similar in at least one important respect suggesting that these drugs may share a common site of action.

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Behaviorally induced sensitivity to the discriminable properties of LSD.

Rats were initially trained to discriminate LSD from saline in two-lever operant chambers by reinforcing responses only on one lever following intraperitoneal injections of 80 mug/kg of LSD and only on the other lever following saline injections. Choice responding during extinction periods (no water reinforcement for either response) indicated a high level of discriminability (95% correct) following either LSD or saline. A dose-response curve for LSD, obtained by tests for lever choice after injections of 10, 20, 30, 40, 50, and 60 mug/kg, indicated that 10 mug/kg produced only 30% responding on the LSD lever. This percentage was increased (to 83%) by reinforcing responding on the LSD lever following injections of 10 mug/kg. Subsequent tests indicated that doses of 5.0 and 2.5 mug/kg produced a majority of responses on the LSD lever. Since at these low doses LSD has few measurable biochemical or behavioral effects, we hypothesized that the discriminable cue of LSD is related to direct stimulation of central serotonergic receptors.

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Conditioned suppression of bar-pressing behavior by stimuli associated with drugs.

Ten naive male albino rats were trained to press a bar under a variable-interval 30-sec schedule with water as the reinforcer in two experiments. This behavior was disrupted by chlorpromazine in Experiment I (two rats) and by lysergic acid diethylamide (LSD) in both Experiment I (two rats) and Experiment II (six rats). The administration of the drug was paired with an originally neutral white light. After several pairings with either drug, the light also depressed behavior. When the light was no longer paired with drug, the depression effect extinguished much faster than is usually observed in conditioned suppression studies.

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