Apomorphine priming alters the response of striatal outflow pathways to D2 agonist stimulation in 6-hydroxydopamine-lesioned rats

Pollack, Alexia E.; Turgeon, Sarah M.; Fink, J. Stephen

doi:10.1016/s0306-4522(96)00681-1

Cited by 34 publications

(25 citation statements)

References 72 publications

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“…Interestingly, Pollack et al (1997) showed that "priming" by the dopamine agonist apomorphine leads to the recruitment of D 2 receptorexpressing in concert with D 1 receptor-expressing striatal neurons to produce enhanced behavioral and cellular responses. Similarly, in striatal slices, activation of the D 2 or A 2A receptors transynaptically interacts with D 1 receptors to modulate phosphorylation of DARPP-32, an effect that was blocked by tetrodotoxin (Lindskog et al, 1999).…”

Section: Potential Mechanisms By Which the A 2a Receptor Facilitates mentioning

confidence: 99%

Persistent Behavioral Sensitization to Chronic l-DOPA Requires A_2AAdenosine Receptors

et al. 2002

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To investigate the role of A 2A adenosine receptors in adaptive responses to chronic intermittent dopamine receptor stimulation, we compared the behavioral sensitization elicited by repeated L-DOPA treatment in hemiparkinsonian wild-type (WT) and A 2A adenosine receptor knock-out (A 2A KO) mice. Although the unilateral nigrostriatal lesion produced by intrastriatal injection of 6-hydroxydopamine was indistinguishable between WT and A 2A KO mice, they developed strikingly different patterns of behavioral sensitization after daily treatment with low doses of L-DOPA for 3 weeks. WT mice initially displayed modest contralateral rotational responses and then developed progressively greater responses that reached a maximum within 1 week and persisted for the duration of the treatment. In contrast, any rotational behavioral sensitization in A 2A KO mice was transient and completely reversed within 2 weeks. Similarly, the time to reach the peak rotation was progressively shortened in WT mice but remained unchanged in A 2A KO mice. Furthermore, daily L-DOPA treatment produced gradually sensitized grooming in WT mice but failed to induce any sensitized grooming in A 2A KO mice. Finally, repeated L-DOPA treatment reversed the 6-OHDA-induced reduction of striatal dynorphin mRNA in WT but not A 2A KO mice, raising the possibility that the A 2A receptor may contribute to L-DOPA-induced behavioral sensitization by facilitating adaptations within the dynorphinexpressing striatonigral pathway. Together these results demonstrate that the A 2A receptor plays a critical role in the development and particularly the persistence of behavioral sensitization to repeated L-DOPA treatment. Furthermore, they raise the possibility that the maladaptive dyskinetic responses to chronic L-DOPA treatment in Parkinson's disease may be attenuated by A 2A receptor inactivation. Key words: A 2A adenosine receptor; L-DOPA; behavioral sensitization; Parkinson's disease; dyskinesia; dynorphinFor Ͼ30 years the dopamine precursor L-DOPA has been the most effective and commonly prescribed treatment for Parkinson's disease (PD). Despite its considerable symptomatic motor benefit, chronic administration of L-DOPA leads to abnormal motor responses known as dyskinesias, involving involuntary choreic or dystonic movements in Ͼ50% of patients (5 years after the initiation of the treatment) (Chase, 1998;Obeso et al., 2000). Such shortcomings of L-DOPA and other dopaminergic drugs have prompted a search for alternative treatment strategies that provide symptomatic benefits while avoiding the delayed motor complications associated with the long-term use of antiparkinsonian drugs. Several neurotransmitters have been implicated in the motor complications elicited by repeated dopamine receptor stimulation, including glutamate (Marin et al., 1996;Tzschentke and Schmidt, 1998;Calabresi et al., 2000), cannabinoids (Souilhac et al., 1995;Zeng et al., 1999), opioids (Henry and Brotchie, 1996), and adenosine (Richardson et al., 1997;Kanda et al., 2000;Jenner, 2000). Recent...

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Section: Potential Mechanisms By Which the A 2a Receptor Facilitates mentioning

confidence: 99%

Persistent Behavioral Sensitization to Chronic l-DOPA Requires A_2AAdenosine Receptors

et al. 2002

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“…This finding shows that apomorphine may affect activation patterns, normally induced by mating or matingrelated cues. The questions about direct "priming" (Pollack et al, 1997) and/or "sensitization" effects (Laudrup et al, 1997;Saka et al, 1999) of apomorphine playing a role here, remain to be addressed in more specific experiments. In our view, indirect effects on reward and arousal processes induced by sexassociated environmental cues (Balfour et al, 2004;Sachs, 2000) most probably play an important role.…”

Section: Apo-sex-interactive Brain Areasmentioning

confidence: 97%

Effects of acute and chronic apomorphine on sex behavior and copulation-induced neural activation in the male rat

Olivier

Jong

Dederen

et al. 2007

European Journal of Pharmacology

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Apomorphine is a non-selective dopaminergic receptor agonist. Because of its pro-erectile effects, apomorphine is clinically used for treatment of erectile dysfunction. We investigated the effects of subcutaneous apomorphine administration (0.4 mg/kg rat) on sexual behavior and matinginduced Fos-expression following acute (day 1) or chronic apomorphine treatment (days 8 and 15) in sexually experienced male rats. Consistent facilitatory effects of apomorphine were observed in the reduced numbers of mounts and intromissions over time and an increased ejaculation frequency on day 1. The first post-ejaculatory interval, however, was lengthened, while other behavioral parameters were unaffected. Fosimmunoreactivity induced by acute apomorphine administration (barrel cortex, paraventricular hypothalamic nucleus, central amygdala and locus coeruleus) was strongly reduced after chronic administration. After mating, induction of Fos-immunoreactivity was observed in well-known areas like medial preoptic nucleus and the posterodorsal medial amygdaloid area. Apomorphine, however, reduced mating-induced Fosimmunoreactivity in the nucleus accumbens shell and prevented its occurrence in its core area. This remarkable apomorphine effect was not observed in any other brain area. We conclude that the behavioral (pro-erectile) effects of apomorphine are consistent over time, and that the diminished accumbens-Fos-immunoreactivity and the elongated post-ejaculatory interval may reflect a decreased response to remote cues from the estrus female.

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“…Male Sprague-Dawley rats (275-305 g) were anesthetized with ketamine (50 mg/kg):xylazine (6 mg/kg), and injected with desmethylimipramine (25 mg/kg) in order to block norepinephrine reuptake prior to a stereotaxic injection of the neurotoxin 6-OHDA (3 mg/ml) and ascorbic acid (2 mg/ml) dissolved in saline into the medial forebrain bundle (coordinates from bregma: -3.7 AP, +1.6 ML, -8.8 DV) [22] as described previously [17] . All efforts were made to minimize pain and discomfort in experimental animals.…”

Section: -Hydroxydopamine Lesionsmentioning

confidence: 99%

“…Brains were frozen, and 60-m coronal sections were cut using a sliding microtome. Brain sections through the striatum were processed for immunohistochemistry using a tyrosine hydroxylase (TH) antibody (1: 1,000 dilution; Pel-Freez, Rogers, Ark., USA), as described previously [17,18] , in order to verify dopamine depletion. TH-stained brain sections from all groups were qualitatively scored by comparing them to TH-stained sections from 6-OHDA rats treated with the D1 dopamine agonist SKF38393 (10 mg/kg, n = 6, positive control), which displayed robust contralateral rotational behavior corresponding to 1 95% dopamine depletion [18] .…”

Section: Immunohistochemistrymentioning

confidence: 99%

“…For example, we have found that pretreatment (priming) with 3 injections, spaced 3-6 days apart, of D1, D2 or D1/D2 dopamine agonists permits a behaviorally ineffective dose of the D2 agonist quinpirole (0.25 mg/kg) to produce robust contralateral rotational behavior in 6-OHDA rats, suggesting that prior exposure to a dopamine agonist greatly influences the subsequent behavioral response following challenge with a D2 agonist [17,18] . While some of the acute behavioral effects of caffeine in 6-OHDA rats have been characterized [10,11,13] , less is known about the role of caffeine in sensitizing (priming) dopamine-mediated behaviors in 6-OHDA rats.…”

Section: Introductionmentioning

confidence: 99%

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Prior Treatment (Priming) with Caffeine Sensitizes D2-Dopamine-Mediated Contralateral Rotational Behavior in 6-Hydroxydopamine-Lesioned Rats

Pollack

Dimitrov²,

Drake³

2010

Pharmacology

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Background/Aims: In unilaterally dopamine-depleted rats, repeated treatment with dopamine agonists sensitizes contralateral rotational behavior. Since A2a adenosine receptors are co-localized with D2 dopamine receptors in the brain, it was hypothesized that repeated treatment with the adenosine antagonist caffeine could sensitize D2 dopamine-mediated rotational behavior. Methods: Rats were unilaterally lesioned with 6-hydroxydopamine (6-OHDA), and pretreated (primed) with 3 injections of caffeine or water. One week later, rats were challenged with the D2 agonist quinpirole (0.25 mg/kg). Results: 6-OHDA rats primed with caffeine (50 mg/kg) displayed contralateral rotational behavior following challenge with quinpirole – an effect not observed with caffeine (10 or 75 mg/kg) or water. Conclusions: These results suggest that prior administration of caffeine can sensitize D2 dopamine-mediated rotational behavior in dopamine-depleted rats.

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Apomorphine priming alters the response of striatal outflow pathways to D2 agonist stimulation in 6-hydroxydopamine-lesioned rats

Cited by 34 publications

References 72 publications

Persistent Behavioral Sensitization to Chronic l-DOPA Requires A_2AAdenosine Receptors

Persistent Behavioral Sensitization to Chronic l-DOPA Requires A_2AAdenosine Receptors

Effects of acute and chronic apomorphine on sex behavior and copulation-induced neural activation in the male rat

Prior Treatment (Priming) with Caffeine Sensitizes D2-Dopamine-Mediated Contralateral Rotational Behavior in 6-Hydroxydopamine-Lesioned Rats

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Apomorphine priming alters the response of striatal outflow pathways to D2 agonist stimulation in 6-hydroxydopamine-lesioned rats

Cited by 34 publications

References 72 publications

Persistent Behavioral Sensitization to Chronic l-DOPA Requires A2AAdenosine Receptors

Persistent Behavioral Sensitization to Chronic l-DOPA Requires A2AAdenosine Receptors

Effects of acute and chronic apomorphine on sex behavior and copulation-induced neural activation in the male rat

Prior Treatment (Priming) with Caffeine Sensitizes D2-Dopamine-Mediated Contralateral Rotational Behavior in 6-Hydroxydopamine-Lesioned Rats

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Persistent Behavioral Sensitization to Chronic l-DOPA Requires A_2AAdenosine Receptors

Persistent Behavioral Sensitization to Chronic l-DOPA Requires A_2AAdenosine Receptors