Repeated administration of caffeine induces either sensitization or tolerance of locomotor stimulation depending on the environmental context

Zancheta, Roberta; Possi, Ana P. M.; Planeta, Cleópatra da Silva; Marin, Marcelo Tadeu

doi:10.1016/s1734-1140(12)70732-6

Cited by 16 publications

(9 citation statements)

References 46 publications

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“…With regards to caffeine, although it acutely increased activity consistent with previous reports (Buckholtz and Middaugh, 1987; Hilbert et al , 2013; Kaplan et al , 1989), repeated exposure to caffeine did not produce locomotor sensitization in our model. While several other reports indicate that caffeine can induce a small, albeit significant, locomotor sensitization effect (Ball and Poplawsky, 2011; Hsu et al , 2009; Hsu et al , 2010; Zancheta et al , 2012), the reason for the lack of caffeine locomotor sensitization in our model is unclear but may be related to methodological differences such as dose, route of administration and frequency of administration.…”

Section: Discussionmentioning

confidence: 59%

Sensitization and Tolerance Following Repeated Exposure to Caffeine and Alcohol in Mice

May

Haun

Griffin

2015

Alcohol Clin Exp Res

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Introduction Energy drinks are popular mixers with alcohol. While energy drinks contain many ingredients, caffeine is an important pharmacologically active component and is generally present in larger amounts than in other caffeinated beverages. In these studies, we investigated the hypothesis that caffeine would influence the effects of alcohol (ethanol) on conditioned taste aversion, ataxia and locomotor activity after repeated exposure. Methods Four groups of mice were exposed by oral gavage twice daily to vehicle, ethanol (4 g/kg), caffeine (15 mg/kg), or the ethanol/caffeine combination. Conditioned taste aversion to saccharin and ataxia in the parallel rod task were evaluated after 8 or 16 gavages, respectively, using ethanol (1–3 g/kg) or ethanol/caffeine (3mg/kg + 2 g/kg) challenges. In addition, locomotor activity was evaluated initially and after repeated exposure to oral gavage of these drugs and doses. Results Repeated oral gavage of ethanol produced significant locomotor sensitization, with those mice increasing total distance traveled by 2-fold. The locomotor response to caffeine, while significantly greater than vehicle gavage, did not change with repeated exposure. On the other hand, repeated gavage of caffeine/ethanol combination produced a substantial increase in total distance traveled after repeated exposure (~4-fold increase). After repeated ethanol exposure, there was significant tolerance to ethanol in the conditioned taste aversion and parallel rod tests. However, neither a history of caffeine exposure nor including caffeine influenced ethanol-induced conditioned taste aversion. Interestingly, a history of caffeine exposure increased the ataxic response to the caffeine/ethanol combination and appeared to reduce the ataxic response to high doses of ethanol. Conclusion The data support the general hypothesis that repeated exposure to caffeine influences the response to ethanol. Together with previously published work, these data indicate that caffeine influences some ethanol-related behaviors, notably locomotion and ataxia, but appears not to influence the expression of conditioned behaviors.

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Section: Discussionmentioning

confidence: 59%

Sensitization and Tolerance Following Repeated Exposure to Caffeine and Alcohol in Mice

May

Haun

Griffin

2015

Alcohol Clin Exp Res

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“…This phenomenon was observed after repeated administration of both legal and illegal drugs and has been described for ethanol (Broadbent 2013;Kim and Souza-Formigoni 2013;Linsenbardt and Boehm 2013), nicotine (Hamilton et al 2012;Lenoir et al 2013;Perna and Brown 2013), caffeine (Zancheta et al 2012), cannabinoids (Rubino et al 2003;Cadoni et al 2008), psycho-stimulants (Landa et al 2006a,b;2012a,b;Wang et al 2010;Ball et al 2011;Kameda et al 2011) or opioids (Bailey et al 2010;Liang et al 2010;Farahmandfar et al 2011;Hofford et al 2012;Rezayof et al 2013).…”

mentioning

confidence: 81%

The effect of the cannabinoid CB1 receptor agonist arachidonylcyclopropylamide (ACPA) on behavioural sensitisation to methamphetamine in mice

Landa¹,

Šlais²,

Máchalová³

et al. 2014

Vet. Med. - Czech

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ABSTRACT:The psychostimulant methamphetamine (Met), similarly to other drugs of abuse, is known to produce an increased behavioural response after its repeated application (behavioural sensitisation). It has also been described that an increased response to a drug may be elicited by previous repeated administration of another drug (cross-sensitisation). We have previously shown that the CB 1 , CB 2 and TRPV (vanilloid) cannabinoid receptor agonist methanandamide, cross-sensitised to Met stimulatory effects in mice. The present study was focused on ability of the more selective and potent CB 1 receptor activator arachidonylcyclopropylamide (ACPA) to elicit cross-sensitisation to the stimulatory effects of Met on mouse locomotor behaviour in the Open field test. Male mice were randomly divided into three groups and on seven occasions (from the 7 th to 13 th day of the experiment) were administered drugs as follows:(a) n 1 : vehicle at the dose of 10 ml/kg/day; (b) n 2 : Met at the dose of 2.5 mg/kg/day; (c) n 3 : ACPA at the dose of 1.0 mg/kg/day. Locomotor behaviour in the Open field test was measured (a) after administration of vehicle on the 1 st experimental day, (b) after the 1 st dose of drugs given on the 7 th day, and (c) on the 14 th day after the "challenge doses" administered in the following manner: n 1 : saline at a dose of 10 ml/kg, n 2, 3 : Met at a dose of 2.5 mg/kg. The observed behavioural changes consisted in: (a) gradual development of habituation to the open field conditions in three consecutive tests; (b) development of behavioural sensitisation to the stimulatory effects of Met after repeated treatment; (c) insignificant effect of repeated pre-treatment with ACPA on the stimulatory effects of Met challenge dose. The results of our study give rise to the question which of the cannabinoid receptor mechanisms might be most responsible for the neuroplastic changes inducing sensitisation to the stimulatory effects of Met. Keywords

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“…The phenomenon extends to all addictive drugs, with their dependence on dopaminergic mechanisms, and it has been suggested to be involved in the development of drug addiction (Kalivas and Steward 1991; Robinson et al 1998). Again, non-tolerance-associated continuous caffeine exposure (low caffeine concentration in the drinking water) or repeated intermittent caffeine administration induces environment-dependent sensitization to its psychomotor effects and cross-sensitization to direct and indirect dopamine receptor agonists, such as amphetamine (Gasior et al 2000; Cauli and Morelli 2002; Simola et al 2006; Zancheta et al 2012). On the other hand, strong tolerance develops to the psychostimulant effects of caffeine (including turning behavior in rats with a unilateral 6-OHDA lesion) upon continuous caffeine exposure (high caffeine concentration in the drinking water) or repeated daily (systemic) caffeine administration (Holtzman and Finn 1988; Garrett and Holtzman, 1995b; Howell et al 1997; Karcz-Kubicha et al 2003; Quarta et al 2004a).…”

Section: Psychomotor Activating Effects Of Caffeine: the Striatal Adementioning

confidence: 99%

Mechanisms of the psychostimulant effects of caffeine: implications for substance use disorders

2016

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Background The psychostimulant properties of caffeine are reviewed and compared with those of prototypical psychostimulants, able to cause substance use disorders (SUD). Caffeine produces psychomotor activating, reinforcing and arousing effects, which depend on its ability to disinhibit the brake that endogenous adenosine imposes on the ascending dopamine and arousal systems. Objectives A model that considers the striatal adenosine A2A-dopamine D2 receptor heteromer as a key modulator of dopamine-dependent striatal functions (reward-oriented behavior and learning of stimulus-reward and reward-response associations) is introduced, which should explain most of the psychomotor and reinforcing effects of caffeine. Highlights The model can explain the caffeine-induced rotational behavior in rats with unilateral striatal dopamine denervation and the ability of caffeine to reverse the adipsic-aphagic syndrome in dopamine-deficient rodents. The model can also explain the weaker reinforcing effects and low abuse liability of caffeine, compared with prototypical psychostimulants. Finally the model can explain the actual major societal dangers of caffeine: the ability of caffeine to potentiate the addictive and toxic effects of drugs of abuse, with the particularly alarming associations of caffeine (as adulterant) with cocaine, amphetamine derivatives and synthetic cathinones and energy drinks with alcohol; and the higher sensitivity of children and adolescents to the psychostimulants effects of caffeine and its possible increase in the vulnerability to develop SUD. Conclusions The striatal A2A-D2 receptor heteromer constitutes an unequivocal main pharmacological target of caffeine and provides the main mechanisms by which caffeine potentiates the acute and long-term effects of prototypical psychostimulants.

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Repeated administration of caffeine induces either sensitization or tolerance of locomotor stimulation depending on the environmental context

Cited by 16 publications

References 46 publications

Sensitization and Tolerance Following Repeated Exposure to Caffeine and Alcohol in Mice

Sensitization and Tolerance Following Repeated Exposure to Caffeine and Alcohol in Mice

The effect of the cannabinoid CB1 receptor agonist arachidonylcyclopropylamide (ACPA) on behavioural sensitisation to methamphetamine in mice

Mechanisms of the psychostimulant effects of caffeine: implications for substance use disorders

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