Tolerance to the behavioral effects of marihuana in chimpanzees

Ferraro, Douglas P.; Grisham, Michael G.

doi:10.1016/0031-9384(72)90263-6

Cited by 30 publications

(5 citation statements)

References 19 publications

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“…The fact that the second administration of 0.25 mg/kg A9-THC failed to reach statistical significance suggests the possibility that some tolerance to A%TI-IC developed across successive exposures to the drug (e.g., Ferraro and Grisham, 1972;McMillan, Harris, Frankenheim and Kennedy, 1970). However, no marked longterm effects of A9-TtIC on variable interval responding were apparent as evidenced by the overall stability of the baseline schedule and by the almost complete recovery of predrug response rates during the first postdrug session at each Ag-THC dose used.…”

Section: Resultsmentioning

confidence: 99%

Biphasic effects of ?9-tetrahydrocannabinol on variable interval schedule performance in rats

Grisham

Ferraro

1972

Psychopharmacologia

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Abstract. Four rats were trained to barpress for water reinforcement under a variable interval 60 sec schedule. 1XTine acute administrations of (--)Ag-trans-tetrahydrocannabinol, in amounts ranging from 0.25 to 16.0 mg/kg, produced doserelated effects on responding; overall response rate increased at lower doses, while higher doses produced ataxia and a complete suppression of responding. Increased response rates reflected changes both in response spacing and in the lengths of postreinforcement pauses. It was concluded that marihuana has a biphasic effect on variable interval water-reinforced behavior in rats. Key words: Marihuana (Cannabis) --(--)39-trans-Tetrahydrocannabinol(Ag-TttC) --Psychopharmacology --Operant Behavior --Schedule of Reinforcement.Both the unconditioned behavior and conditioned shock avoidance behavior of animals have been shown to be either increased or decreased by marihuana or a tetrahydroeannabinol (THC) derivative (e.g., Barry and Kubena, 1971 ; Garriott, King, Forney and Hughes, 1967;Holtzman, Lovell, Jaffe and Freedman, 1969;Kubena and Barry, 1970; Seheckel, Boff, Dahlen and Smart, 1968). A greater consistency between findings has been obtained with simple appetitive reinforcement operant conditioning schedules where the usual effect of marihuana has been to suppress the ongoing rate of response in rats and pigeons (e.g

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Section: Resultsmentioning

confidence: 99%

Biphasic effects of ?9-tetrahydrocannabinol on variable interval schedule performance in rats

Grisham

Ferraro

1972

Psychopharmacologia

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“…The results from the present study also add to the small amount of existing data in the literature involving either monkeys or humans showing that tolerance develops to the disruptive effects of Δ 9 -THC on transitional behaviors or learning (see Thompson & Moerschbaecher, 1979). In nonhuman primates, for example, most of the studies examining the development of tolerance have used steady-state operant behaviors (e.g., Beardsley, Balster, & Harris, 1984; Branch et al, 1980; Elsmore, 1972; Ferraro & Grisham, 1972), and none, to our knowledge, have used a learning task. The same is true for the studies involving other animal species (e.g., Lamb, Jarbe, Makriyannis, Lin, & Goutopoulos, 2000; McMillan, Hardwick, & Wells, 1983), with only a few exceptions (Delatte et al, 2002; McMillan, 1988).…”

Section: Discussionmentioning

confidence: 99%

Tolerance to chronic delta-9-tetrahydrocannabinol (Δ⁹-THC) in rhesus macaques infected with simian immunodeficiency virus.

Winsauer

Molina

Amedee

et al. 2011

Experimental and Clinical Psychopharmacology

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Although Δ9-THC has been approved to treat anorexia and weight loss associated with AIDS, it may also reduce well-being by disrupting complex behavioral processes or enhancing HIV replication. To investigate these possibilities, four groups of male rhesus macaques were trained to respond under an operant acquisition and performance procedure, and administered vehicle or Δ9-THC before and after inoculation with simian immunodeficiency virus(SIVmac251, 100 TCID50/ml, i.v.). Prior to chronic Δ9-THC and SIV inoculation, 0.032– 0.32 mg/kg of Δ9-THC produced dose-dependent rate-decreasing effects and small, sporadic error-increasing effects in the acquisition and performance components in each subject. Following 28 days of chronic Δ9-THC (0.32 mg/kg, i.m.) or vehicle twice daily, delta-9-THC-treated subjects developed tolerance to the rate-decreasing effects, and this tolerance was maintained during the initial 7–12 months irrespective of SIV infection (i.e., +THC/−SIV, +THC/+SIV). Full necropsy was performed on all SIV subjects an average of 329 days post-SIV inoculation, with postmortem histopathology suggestive of a reduced frequency of CNS pathology as well as opportunistic infections in delta-9-THC-treated subjects. Chronic Δ9-THC also significantly reduced CB-1 and CB-2 receptor levels in the hippocampus, attenuated the expression of a proinflammatory cytokine (MCP-1), and did not increase viral load in plasma, cerebrospinal fluid, or brain tissue compared to vehicle-treated subjects with SIV. Together, these data indicate that chronic Δ9-THC produces tolerance to its behaviorally disruptive effects on complex tasks while not adversely affecting viral load or other markers of disease progression during the early stages of infection.

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“…The best studied is rebound in the integrated electrocorticogram of the rat (177), an effect reaching its maximum 2-6 days after cessation of drug, and returning to normal in 12-17 days. In addition, a performance decrement (but no other abstinence signs) has been noted in chimpanzees on DRL or delayed matching schedules (184,186). Rebound rapid eye movement (REM) sleep is mentioned in a later section.…”

Section: Tolerance and Withdrawal Effectsmentioning

confidence: 98%

“…The development of tolerance continues to be reported for most effects of cannabis and f11_ THC: these in v olve performance of rats on a rotating rod or a balance beam pigeon pecking fo r fo od reward (178,179), effects in the frog (179a), catalepsy in mice (180), effects on sleep in rats (181), elevation of blood corticosterone levels in mice (180), rat bar pressing fo r fo od (182), and DRL (differential reinforcement of low rates) schedules in monkeys (183,184). Neurophysiological responses to which tolerance occurs include the anticonvulsant effect and depression of () waves in the hippocampus (l42a), and the reduction in the integrated electrocorticogram of rat (177).…”

Section: Tolerance and Withdrawal Effectsmentioning

confidence: 99%

Pharmacology of Marijuana

Patón¹

1975

Annu. Rev. Pharmacol.

114

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·: ·6617This review is concerned primarily with the papers that have appeared since the end of 1972 subsequent to the material in the book by Nahas (1) and the review volumes edited by Mechoulam (2) and by Gibbins et al (3). The main new developments have been in the biochemistry of cannabis metabolites, in cellular and toxicological effects, and in a widening of human studies. CHEMICAL ASPECTSStructure-Action Relationships (4,5,6) Variations in potency among cannabinoids by a factor of over 2000 are now recorded, which allow considerable scope for structure-action studies. But estimates of relative potency remain difficult to make because of the variability among subjects (whether animals or humans). At a deeper level, little work has been done to assess how far variations in potency reflect differences in pharmacokinetics or in metabo lism (with possible formation both of active and inactive metabolites), as against differences in effect at the ultimate site(s) of action. In addition, many of the structures involved have several isomers and are usually tested as mixtures. Finally, pharmacological study has not been sufficiently detailed to exclude major differences in type of action between the various substances. This may be important, since trial of I, l-dimethylheptyl-�3-THC (DMHP) in man showed that, while it produces pronounced tachycardia and hypotension in man, it has no psychic effect (7). The same may be true of other compounds tested only in animals.Subject to these qualifications, the following provisional generalizations may be made, characterizing the tetrahydrocannabinol (THC) molecule as possessing three rings, terpenoid, pyran, and aromatic and using the terpenoid nomenclature.

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Tolerance to the behavioral effects of marihuana in chimpanzees

Cited by 30 publications

References 19 publications

Biphasic effects of ?9-tetrahydrocannabinol on variable interval schedule performance in rats

Biphasic effects of ?9-tetrahydrocannabinol on variable interval schedule performance in rats

Tolerance to chronic delta-9-tetrahydrocannabinol (Δ⁹-THC) in rhesus macaques infected with simian immunodeficiency virus.

Pharmacology of Marijuana

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