Sustained improvement of motor function in hemiparkinsonian rats chronically treated with low doses of caffeine or trihexyphenidyl

  title={Sustained improvement of motor function in hemiparkinsonian rats chronically treated with low doses of caffeine or trihexyphenidyl},
  author={Jos{\'e} L. Bata-Garc{\'i}a and Jairo Villanueva-Toledo and Gabriel Guti{\'e}rrez-Ospina and Fernando Jos{\'e} {\'A}lvarez-Cervera and Francisco J. Heredia-L{\'o}pez and Jos{\'e}L. G{\'o}ngora-Alfaro},
  journal={Pharmacology Biochemistry and Behavior},
The effects of chronic oral treatment with low doses of caffeine (1-3 mg/kg) and trihexyphenidyl (0.1-0.2 mg/kg) were tested on hemiparkinsonian rats, which received the following treatments in a counterbalanced order: vehicle, caffeine, trihexyphenidyl, and caffeine plus trihexyphenidyl. Three preclinical models were used: the stepping test, the cylinder test, and the staircase test. Compared to pre-lesion values, the forepaw contralateral to the dopamine-denervated side showed impaired… Expand
Improvement of postural adjustment steps in hemiparkinsonian rats chronically treated with caffeine is mediated by concurrent blockade of A1 and A2A adenosine receptors
It is suggested that the improvement of postural adjustments induced by chronic treatment with low doses of caffeine in hemiparkinsonian rats is mediated by concurrent blockade of A1 and A2A adenosine receptors, with a larger involvement of the latter. Expand
Caffeine has greater potency and efficacy than theophylline to reverse the motor impairment caused by chronic but not acute interruption of striatal dopaminergic transmission in rats
It is suggested that caffeine would provide more benefits than theophylline to improve the motor function in patients with Parkinson's disease because of their comparable potencies and attaining the maximal effect at similar doses. Expand
Green Coffee Extract Blockades Haloperidol-Induced Catalepsy and Contralateral Rotations Induced by Apomorphine After Unilateral 6-OHDA Lesion on Striatum
Epidemiological studies have shown an inverse association between coffee consumption and the development of Parkinson’s disease (PD). The present investigation aimed to evaluate the effects ofExpand
Green coffee extract attenuates Parkinson's-related behaviors in animal models.
The results indicate that CE components indirectly modulate dopaminergic transmission, suggesting a pro-dopaminergic action of CE, and further investigation must be conducted to elucidate the mechanisms of action and the possible neuroprotective role in PD. Expand
Effect of acute trihexyphenidyl abuse on rat motor area of cerebral cortex: light and electron microscopic study
TPH induced dose-dependent structural changes in rat frontal cortex motor area and therefore, THP prescription must be under strict supervision. Expand
Chronic feeding with 3% dried raw blueberries (V. corymbosum) reduces apomorphine-induced rotations and striatal dopaminergic loss in hemiparkinsonian rats.
The consumption of 3% dried raw blueberries attenuates dopaminergic denervation and partially reverses motor disorders in the 6-OHDA-induced PD model in rats, and anthocyanins in BB methanolic extracts neutralized the free radical 2,2-diphenyl-1-picrylhydrazyl in a concentration-dependent manner. Expand
Interactions between adenosine and dopamine receptor antagonists with different selectivity profiles: Effects on locomotor activity
Forebrain dopamine (DA) is a critical component of the brain circuitry regulating behavioral activation. Adenosine A(2A) antagonists reverse many of the behavioral effects of DA antagonists, andExpand
Closing the gap between clinic and cage: Sensori-motor and cognitive behavioural testing regimens in neurotoxin-induced animal models of Parkinson's disease
Toxin models of PD have and continue to be important models to use for understanding the consequences of nigrostriatal dopamine cell loss, and tests assessing sensorimotor and cognitive function, both of which are significantly and progressively impaired in PD are focused on. Expand
Portable microstimulator for chronic deep brain stimulation in freely moving rats
This first data demonstrated that long term DBS procedure in behaving rat is now workable, and it is shown that this long duration stimulation reduces significantly PD-induced akinesia without inducing animal discomfort and tissue damage. Expand
Potential Role of Caffeine in the Treatment of Parkinson’s Disease
Emerging evidence suggests that caffeine may reduce parkinsonian motor symptoms by antagonising the adenosine A2A receptor, which is predominately expressed in the basal ganglia, and caffeine may be used as an adjuvant in treating PD. Expand


Treatment with subthreshold doses of caffeine plus trihexyphenidyl fully restores locomotion and exploratory activity in reserpinized rats
The proposal that low, subthreshold doses of caffeine plus THP have the potential to alleviate the motor disabilities in parkinsonian patients, with a low risk of causing anxiety or memory impairment is supported. Expand
Scopolamine prevents tolerance to the effects of caffeine on rotational behavior in 6-hydroxydopamine-denervated rats.
Findings strongly suggest that muscarinic cholinergic processes may be involved in tolerance to caffeine-induced contralateral turning, and are interpreted in terms of the possible interactions between dopamine, adenosine and acetylcholine neurotransmitter systems within the basal ganglia circuitry involved in motor behavior. Expand
Properties of rotational behaviour produced by methylxanthine derivatives in mice with unilateral striatal 6-hydroxydopamine-induced lesions.
The results suggest that methylxanthine derivatives produce contralateral rotational behaviour due to not only phosphodiesterase inhibition but also dopamine receptor stimulation. Expand
Caffeine produces contralateral rotation in rats with unilateral dopamine denervation: comparisons with apomorphine-induced responses
Like the dopamine agonist apomorphine, the methylxanthines caffeine, theophylline and theobromine produced dose-dependent contralateral rotation in rats with unilateral 6-hydroxydopamine denervation,Expand
Comparison of the effects of prototypical behavioral stimulants on locomotor activity and rotational behavior in rats
There was a significant correlation of the effects of the three prototypical behavioral stimulants that interact with dopamine systems via different mechanisms of action with effects on locomotor activity, but effects across drugs were not identical. Expand
Caffeine and muscarinic antagonists act in synergy to inhibit haloperidol-induced catalepsy
It is indicated that low doses of caffeine enhance the anticataleptic actions of muscarinic antagonists, and the possibility of using caffeine as adjunctive therapy to reduce the doses and the adverse effects of anticholinergics in Parkinson's disease is left open. Expand
Cross-sensitization between caffeine- and l-dopa-induced behaviors in hemiparkinsonian mice
Cross-sensitization between caffeine and L-dopa following repeated treatment and their positive interaction during chronic co-adminstration in hemiparkinsonian mice suggest that repeated exposure to caffeine may alter L-Dopa responses in PD. Expand
Forelimb akinesia in the rat Parkinson model: differential effects of dopamine agonists and nigral transplants as assessed by a new stepping test
The experiments reported here evaluate the usefulness of a new “stepping test” to monitor forelimb akinesia in rats with unilateral 6-hydroxydopamine lesions of the mesencephalic dopamine (DA) system, and assess the ability of DA- receptor agonists and fetal DA neuron transplants to reverse these deficits. Expand
Motor stimulant effects of caffeine in 6‐hydroxydopamine‐lesioned rats are dependent on previous stimulation of dopamine receptors: a different role of D1 and D2 receptors
Caffeine does not induce any contralateral rotation in drug‐naive 6‐hydroxydopamine‐lesioned rats, and priming with a dopamine agonist enables caffeine to induce contralsateral rotation, this rotation is, however, context independent only after primed with a selective D1 agonist. Expand
Tolerance to oral and IP caffeine: Locomotor activity and pharmacokinetics
  • C. Lau, J. Falk
  • Medicine
  • Pharmacology Biochemistry and Behavior
  • 1994
Locomotor activity increase was a bitonic function of acute caffeine IP doses (2.5-40 mg/kg) in rats and a linear relation between locomotor activity and serum caffeine concentration was obtained after oral self-administration. Expand