ANTAGONISM OF THE EFFECTS ON THERMOREGULATION OF Δ<sup>9</sup>‐TETRAHYDROCANNABINOL BY CLOMIPRAMINE IN THE RAT

Fennessy, M. R.; Taylor, Dorothy

doi:10.1111/j.1476-5381.1978.tb09756.x

Cited by 24 publications

(10 citation statements)

References 16 publications

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“…The radiotelemetric methods employed also show the temperature effects in the first several hours after dosing uncontaminated by chair restraint of the animals although in this case it appears that such methodological differences do not play a major role for the effects observed from about 1–6 hrs after dosing. These less-invasive techniques also permitted the identification of a moderate hyperthermic effect in the first hour after administration (see inset of Figure 1), consistent with low-dose effects sometimes reported for rodents (Johansson et al, 1975, Fennessy and Taylor, 1978). …”

Section: Discussionsupporting

confidence: 83%

Δ9-Tetrahydrocannabinol attenuates MDMA-induced hyperthermia in rhesus monkeys

Taffe

2012

Neuroscience

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Background Cannabis is commonly consumed by Ecstasy (3,4-methylenedioxymethamphetamine; MDMA) users, including as an intentional strategy to manipulate the drug experience. The most active psychoactive constituent in cannabis, Δ9-tetrahydrocannabinol (THC), and other drugs with partial or full agonist activity at the CB1 receptor, produces a reduction of body temperature in rodents. Reports show that administration of THC can attenuate temperature increases caused by MDMA in mice or rats however a recent study in humans shows that THC potentiates MDMA-induced temperature elevations. Relatively little scientific evidence on the thermoregulatory effects of THC in monkeys is available. Methods The body temperature of male rhesus macaques was recorded after challenge with THC (0.1–0.3 mg/kg, i.m.) or combined challenge of THC with the CB1 receptor antagonist SR141716 (Rimonabant; 0.3 mg/kg, i.m.) or combined challenge of THC (0.1, 0.3 m/gkg, i.m.) with 3,4-methylenedioxymethamphetamine (MDMA; 1.78 mg/kg p.o.) using minimally-invasive, implanted radiotelemetry techniques. Results THC reduced the body temperature of monkeys in a dose-dependent manner with the nadir observed 3–5 hrs post-injection, however an attenuation of normal circadian cooling was also produced overnight following dosing. Hypothermia induced by THC (0.3 mg/kg, i.m.) was prevented by Rimonabant (0.3 mg/kg, i.m.). Finally, 0.3 mg/kg THC (i.m.) attenuated the elevation of body temperature produced by MDMA for about 4 hours after oral dosing. Conclusions As with rodents THC produces a robust and lasting decrement in the body temperature of rhesus monkeys; this effect is mediated by the CB1 receptor. THC also protects against the immediate hyperthermic effects of MDMA in monkeys in a dose-dependent manner. Nevertheless, a paradoxical attenuation of circadian cooling overnight after the THC/MDMA combination cautions that longer term effects may be critical in assessing risks for the recreational user of cannabis in combination with MDMA.

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Section: Discussionsupporting

confidence: 83%

Δ9-Tetrahydrocannabinol attenuates MDMA-induced hyperthermia in rhesus monkeys

Taffe

2012

Neuroscience

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“…This appears to be due to the increase level of extracellular 5‐HT (produced by reuptake inhibition) activating somatodendritic autoreceptors at cell bodies in areas of the raphe nuclei and presynaptic autoreceptors at 5‐HT nerve terminals respectively (Sharp et al , 1997). Therefore, Δ 9 ‐THC may cause the release of 5‐HT in order to produce hypothermia (as was speculated by Fennessy & Taylor [1978]), and the resultant decreased activity of 5‐HT neurones that may be expected following pretreatment with fluoxetine may cause a reduction in the Δ 9 ‐THC‐induced‐hypothermia.…”

Section: Discussionmentioning

confidence: 95%

“…The Δ 9 ‐THC in Intralipid ® emulsion used in this study offers several advantages over previous methods of incorporating Δ 9 ‐THC into a solution. The actions of Δ 9 ‐THC in vivo have previously been investigated by suspending the Δ 9 ‐THC in solution using a suspending agent such as polyvinylpyrrolidone (PVP) (Davies & Graham, 1980; Fennessy & Taylor, 1978). An emulsion has better dissolution characteristics than a suspension as it remains a homogeneous solution even upon standing for extended periods of time.…”

Section: Discussionmentioning

confidence: 99%

“…Several lines of evidence support the view that 5‐HT may be involved in the cannabinoid‐induced hypothermic response. For example, pretreatment with the serotonin selective reuptake inhibitor (SSRI) clomipramine has been shown to modify the hypothermia induced by Δ 9 ‐THC and alter Δ 9 ‐THC‐induced alterations in concentrations of brain 5‐hydroxyindoleacetic acid (5‐HIAA) in the rat (Fennessy & Taylor, 1978). In mice, pretreatment with drugs that alter serotonergic systems such as methysergide, p ‐chlorophenyla‐lanine or clompiramine affected the hypothermic response of Δ 9 ‐THC (Davies & Graham, 1980).…”

Section: Introductionmentioning

confidence: 99%

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Modulation of Δ⁹‐tetrahydrocannabinol‐induced hypothermia by fluoxetine in the rat

Malone

Taylor

1998

British J Pharmacology

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1 It has been suggested that the dose of D 9 -tetrahydrocannabinol (D 9 -THC) that induces hypothermia in the rat increases the release of brain 5-hydroxytryptamine (5-HT). In light of this, we investigated the hypothermia produced by D 9 -THC, and the e ect the selective serotonin reuptake inhibitor¯uoxetine has on this response. 2 A signi®cant dose-dependent decrease in body temperature occurred after i.v. administration of 0.5 to 5 mg kg 71 D 9 -THC; maximum decreases being 0.8+0.28C to 2.9+0.38C. This hypothermic response was attenuated by the cannabinoid CB 1 receptor antagonist SR 141716. 3 Fluoxetine (10 mg kg 71 i.p.) alone caused a decrease in body temperature of 0.6+0.18C (n=32, P50.05) after 40 min. However, pretreatment with¯uoxetine (10 mg kg 71 i.p.) 40 min before D 9 -THC signi®cantly reduced the D 9 -THC-induced hypothermia (n=7 ± 8, P50.05). Contrary to this antagonistlike e ect,¯uoxetine administered 40 min after D 9 -THC signi®cantly potentiated the D 9 -THC-induced hypothermia, producing a maximum decrease of 3.2+0.38C. 4 It is suggested that the e ect of¯uoxetine on the D 9 -THC-induced hypothermic response is dependent on the time of its administration relative to that of D 9 -THC. Pretreatment with¯uoxetine increases extracellular 5-HT due to reuptake inhibition. Increased extracellular 5-HT can activate autoreceptors which may decrease serotonergic activity, thereby reducing the D 9 -THC-induced hypothermia. Conversely, when¯uoxetine is adminstered after D 9 -THC, the reuptake block is thought to potentiate the already activated serotonegic system, hence potentiating the D 9 -THC-induced hypothermia.

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“…The observation that other prostaglandin synthesis inhibitors do not produce hypothermia, whereas A9-THC does, may be explained by the multitude of actions of A9-THC on various neurotransmitters. Previously, the effect of A9-THC on body temperature has been associated with changes in the tryptaminergic (Taylor & Fennessy, 1977;Fennessy & Taylor, 1978) and the noradrenergic (Singh & Das, 1976) systems. It is our hypothesis that A9-THC possesses hypothermic activity by virtue of its action on different neurotransmitters.…”

Section: Discussionmentioning

confidence: 99%

ALTERATION IN THE LEVEL OF ENDOGENOUS HYPOTHALAMIC PROSTAGLANDINS INDUCED BY Δ⁹‐TETRAHYDROCANNABINOL IN THE RAT

Coupar¹,

Taylor²

1982

British J Pharmacology

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Whole brain and regional brain levels of prostaglandin E2 (PGE2)‐like material have been determined following administration of Δ9‐tetrahydrocannabinol (Δ9‐THC) in rats. Intravenous administration of Δ9‐THC 2 mg/kg, resulted in marked behavioural changes and hypothermia. The behavioural changes consisted mainly of catatonia (most apparent at 30 min after administration of Δ9‐THC), followed by sedation (most evident at 60 min). Hypothermia was marked from 30 min after administration of Δ9‐THC. Δ9‐THC did not alter the whole brain levels of PGE2‐like material 30, 60 or 120 min after administration. Δ9‐THC did not alter the levels of PGE2‐like material in the medulla oblongata/pons, midbrain, cortex and cerebellum, 30 min after administration. However, there was a significant reduction of PGE2‐like material in the hypothalamus, 30 min after Δ9‐THC. It is suggested that the Δ9‐THC‐induced decrease in hypothalamic PGE2‐like material may contribute to the hypothermia observed following Δ9‐THC administration.

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ANTAGONISM OF THE EFFECTS ON THERMOREGULATION OF Δ⁹‐TETRAHYDROCANNABINOL BY CLOMIPRAMINE IN THE RAT

Cited by 24 publications

References 16 publications

Δ9-Tetrahydrocannabinol attenuates MDMA-induced hyperthermia in rhesus monkeys

Δ9-Tetrahydrocannabinol attenuates MDMA-induced hyperthermia in rhesus monkeys

Modulation of Δ⁹‐tetrahydrocannabinol‐induced hypothermia by fluoxetine in the rat

ALTERATION IN THE LEVEL OF ENDOGENOUS HYPOTHALAMIC PROSTAGLANDINS INDUCED BY Δ⁹‐TETRAHYDROCANNABINOL IN THE RAT

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ANTAGONISM OF THE EFFECTS ON THERMOREGULATION OF Δ9‐TETRAHYDROCANNABINOL BY CLOMIPRAMINE IN THE RAT

Cited by 24 publications

References 16 publications

Δ9-Tetrahydrocannabinol attenuates MDMA-induced hyperthermia in rhesus monkeys

Δ9-Tetrahydrocannabinol attenuates MDMA-induced hyperthermia in rhesus monkeys

Modulation of Δ9‐tetrahydrocannabinol‐induced hypothermia by fluoxetine in the rat

ALTERATION IN THE LEVEL OF ENDOGENOUS HYPOTHALAMIC PROSTAGLANDINS INDUCED BY Δ9‐TETRAHYDROCANNABINOL IN THE RAT

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ANTAGONISM OF THE EFFECTS ON THERMOREGULATION OF Δ⁹‐TETRAHYDROCANNABINOL BY CLOMIPRAMINE IN THE RAT

Modulation of Δ⁹‐tetrahydrocannabinol‐induced hypothermia by fluoxetine in the rat

ALTERATION IN THE LEVEL OF ENDOGENOUS HYPOTHALAMIC PROSTAGLANDINS INDUCED BY Δ⁹‐TETRAHYDROCANNABINOL IN THE RAT