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B L Jacobs

Publications and source records attributed to B L Jacobs.

At least 163 records · Page 9Linked to original sources
PubMed1977

Behavioral effects of LSD in the cat: proposal of an animal behavior model for studying the actions of hallucinogenic drugs.

In the course of examining the complete dose-response relationship for the behavioral effects of LSD in the cat, we discovered that, in addition to large increases in investigatory and hallucinatory-like responses, two behaviors, not previously reported, are emitted with a high probability under LSD. Beginning from a baseline of essentially zero in saline-treated animals, limb flicks and abortive grooming increase in frequency in direct relation to the dose of LSD administered (2.5, 10, 25 and 50 microgram/kg i.p.) and then decrease at higher doses (100 and 200 microgram/kg). Limb flicks are a species-specific behavior seen in normal cats almost exclusively in response to the presence of a foreign substance, such as water, on the hindpaw or forepaw. In abortive grooming, the cat orients to the body surfaces as if to groom but does not emit the consummatory grooming response (bite, lick or scratch), or emits the response in midair. These behaviors can serve as an animal behavior model for the actions of LSD and related hallucinogens in humans. The specificity of these behavioral changes is indicated by the fact that they are never seen in response to other classes of psychoactive drugs such as D-amphetamine, atropine, caffeine, and cholorpheniramine. They are, however, elicited by compounds such as psilocybin which are structurally and functionally related to LSD. The validity of the model is based on evidence indicating that it is: specific to hallucinogens, dose dependent, observed in a dose range effective in humans, parallels the major parameters of the actions of LSD in humans (see following paper), sensitive, robust, reliable, quantifiable and easy to score.

Animals↗
PubMed1977

Usefulness of an animal behavioral model in studying the duration of action of LSD and the onset and duration of tolerance to LSD in the cat.

LSD elicits a number of emergent behaviors in the cat, including limb flicking, abortive grooming, investigatory and hallucinatory-like behaviors, which we have proposed as an animal behavior model for studying the actions of LSD and related hallucinogens. These emergent behaviors were used in the present study to investigate the duration of action of LSD, as well as the onset and duration of tolerance. A dose of 10 microgram/kg of LSD produced significant behavioral changes for up to 4h, while a dose or 50 microgram/kg produced changes lasting for at least 8 h. Tolerance to a test dose of 50 microgram/kg of LSD is virtually complete one day after a single 50 microgram/kg dose, and lasts for approximately 5 days. Tolerance to a test dose of 50 microgram/kh of LSD one day after a single dose of 10 microgram/kg is quite marked, and lasts for approximately 3 days. A significant tolerance to a test dose of 50 microgram/kg of LSD occurs within 2 h after a single injection of 10 microgram/kg. The limb flick was found to be the most sensitive index in all tests: it showed the longest time-course, as well as the most rapid and longest-lasting tolerance. These studies demonstrate that the LSD-induced behavioral syndrome in the cat parallels important parameters of the action of LSD in humans, and thus enhances the usefulness of the model.

Animals↗
PubMed1977

Comparative effects of hallucinogenic drugs on rotational behavior in rats with unilateral 6-hydroxydopamine lesions.

The dopaminergic actions of various hallucinogenic drugs were assessed by examining their effects on turning behavior in rats with unilateral 6-hydroxydopamine lesions of the nigro-striatal pathway. LSD (0.1 and 0.2 mg/kg) produced strong contralateral turning, indicating that it is a potent dopamine receptor agonist, while BOL (5 mg/kg), a non-hallucinogenic congener of LSD, was found to be a weak dopamine receptor agonist. STP (2 and 5 mg/kg) and mescaline (50 and 100 mg/kg) produced significant ipsilateral turning, indicating that these compounds have a moderate dopamine-releasing action. DMT (10 and 20 mg/kg) and 5-M-DMT (0.75 and 1.25 mg/kg) produced weak ipsilateral turning, which was not significantly different from that produced by the nonhallucinogenic compounds tryptamine (40 mg/kg) or scopolamine (0.25 mg/kg). Psilocin (1-20 mg/kg) produced no significant turning in either direction. These data, in conjunction with previous studies, indicate that while inactivation of the brain serotonin system may be a necessary and sufficient condition for hallucinogenesis, the ability to activate dopamine receptors may be an important factor in determining the potency of hallucinogens.

Animals↗
PubMed1977

A quantitative rotational model for studying serotonergic function in the rat.

Unilateral injection of 5,7-dihydroxytryptamine (4 mug/4 mul) into the medial forebrain bundle of rats produced serotonin depletions of 65% and 70% in the ipsilateral corpus striatum and ipsilateral forebrain, respectively. These animals showed a dose-dependent increase in contralateral turning (rotational behavior) when pretreated with a peripheral decarboxylase inhibitor and then injected with L-5-hydroxytryptophan in doses ranging from 5 to 100 mg/kg i.p. Injections of p-chloroamphetamine, which releases endogenous stores of serotonin, produced ipsilateral turning which could be blocked by prior serotonin depletion. Systemic administration of the catecholamine drugs L-DOPA, apomorphine and D-amphetamine never elicited consistent turning in either direction in these animals. These data indicate that the turning response of rats with unilateral destruction of brain serotonin nerve terminals provides a sensitive tool for quantifiably studying changes in serotonergic function.

5-Hydroxytryptophan↗
PubMed1977

Serotonergic afferents to the dorsal raphe nucleus: evdience from HRP and synaptosomal uptake studies.

Afferent connections of the serotonin (5-HT)-containing dorsal raphe nucleus were investigated in the rat utilizing the horseradish peroxidase (HRP) retrograde cell labeling technique. Small quantities (0.1-0.5 mul) of HRP solutions were infused into the dorsal raphe, and the brains were examined 19-72 h later for retrograde transport of the enzyme. Intrinsic connections within the dorsal raphe nucleus were revealed by this mapping technique, as was an input to the dorsal raphe from another serotonergic cell group, the median raphe nucleus. Little evidence was found for projections from other, more remote, brain sites. A serotonergic innervation of the dorsal raphe was also demonstrated by the presence of high affinity uptake of [3H]5-HT (Km=0.17 muM) into synaptosomal suspensions of the dorsal raphe nucleus. Synaptosomal uptake of [3H]5-HT was blocked by selective destruction of serotonergic axon terminals induced by the intraventricular injection of 200 mug of 5,7-dihydroxytryptamine following desipramine HCl pretreatment, but not by destruction of catecholaminergic axon terminals induced by intraventricularly injected 6-hydroxydopamine (2 X 250 mug). The uptake of [3H]-5-HT by synaptosomes of the dorsal raphe was comparable to that of striatal and hypothalamic synaptosomes, and markedly greater than that of synaptosomes from the cerebellum or nearby dorsal central gray or midbrain reticular formation, indicating the presence of a relatively dense serotonergic innervation. These data together indicate that neurons in the dorsal raphe nucleus receive a prominent serotonergic input that is derived, at least in part, from other neurons within the dorsal nucleus and from a neighboring raphe nucleus.

5,6-Dihydroxytryptamine↗
PubMed1977

Electrophysiological evidence against negative neuronal feedback from the forebrain controlling midbrain raphe unit activity.

The hypothesis that the activity of serotonin (5-HT)-containing neurons of the midbrain raphe is subject to negative neuronal feedback regulation was examined. This hypothesis is based primarily on the observation that the administration of drugs which increase the synaptic availability of 5-HT depress midbrain raphe neuron discharge. Since the preponderance of midbrain raphe efferents are ascending, transections which interrupt both the main efferent outflow, as well as all inputs from anterior levels, ought to disrupt the functional integrity of a neuronal feedback loop. The effect of complete transections of the neuraxis placed just rostral to the midbrain raphe nuclei on the efficacy of two drugs which elevate synaptic serotonin, chlorimipramine and p-chloroamphetamine, was investigated in the chloral hydrate anesthetized rat. Such transections neither blocked nor attenuated the depressive effect of intravenously administered chlorimipramine (0.33 or 0.15 mg/kg) or p-chloroamphetamine (1.25 mg/kg) on midbrain raphe unit discharge. These results suggest that neuronal feedback involving the forebrain dose not mediate the depressive effect of drugs which elevate synaptic serotonin on midbrain raphe neuronal activity. An action at serotonergic synapses intrinsic to the midbrain raphe is suggested as an explanation for the persistence of drug effects in transected animals.

Action Potentials↗
PubMed1976

An animal behavior model for studying the actions of LSD and related hallucinogens.

Cats injected with LSD (d-lysergic acid diethylamide) exhibit a group of behaviors that appear to be specific to hallucinogenic drugs. Two of these behaviors, limb flick and abortive grooming, have an extremely low frequency of occurrence in normal cats, but often dominate the behavior of LSD-treated cats. The frequency of occurrence of this group of behaviors is related to the dose of LSD. The behavioral changes are long-lasting following a single injection of LSD, and exhibit tolerance following the repeated administration of LSD. They are not elicited by a variety of control drugs, but are elicited by other indole nucleus hallucinogens. Because the behavioral effects are specific, reliable, easy to score, and quantifiable, they represent an animal model that can be used in studies of the effects of LSD and related hallucinogens.

Animals↗
PubMed1976

Behavioral evidence for the rapid release of CNS serotonin by PCA and fenfluramine.

Administration of p-chloroamphetamine (PCA) (2.5-10.0 mg/kg) or fenfluramine (FF) (5.0-15.0 mg/kg) to rats induces a behavioral syndrome--consisting of tremor, rigidity, Straub tail, hindlimb abduction, lateral head weaving and reciprocal forepaw treading--which is a reflection of the activity of central serotonin-mediated synapses. The syndrome appears within 3-5 min following i.p. administration of PCA or FF, and the syndrome-inducing effects of PCA and FF are blocked by prior depletion of serotonin with p-chlorophenylalanine. By contrast, the syndrome-inducing effect of 5-methoxy-N,N-dimethyltryptamine (5-M-DMT), which directly stimulates postsynaptic serotonin receptors, is not changed by prior serotonin depletion. Catecholamine depletion with alpha-methyl-p-tyrosine produces essentially no change in the syndrome-inducing effects of PCA, FF or 5-M-DMT. These data indicate that the initial effect of PCA or FF administration is the rapid functional release of stored serotonin.

Amphetamines↗