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Nigrostriatal denervation changes the effect of cannabinoids on subthalamic neuronal activity in rats.

Morera-Herreras T, Ruiz-Ortega JA, Linazasoro G, Ugedo L - Psychopharmacology (Berl.) (2010)

Bottom Line: Conversely, after dopaminergic depletion, WIN 55,212-2, Δ(9)-THC, or anandamide inhibited the STN firing rate without altering its discharge pattern, and stimulatory effects were not observed.Cannabinoids induce different effects on the STN depending on the integrity of the nigrostriatal pathway.These findings advance our understanding of the role of cannabinoids in diseases involving dopamine deficits.

View Article: PubMed Central - PubMed

Affiliation: Department of Pharmacology, Faculty of Medicine, University of the Basque Country, 48940, Leioa, Vizcaya, Spain.

ABSTRACT

Rationale: It is known that dopaminergic cell loss leads to increased endogenous cannabinoid levels and CB1 receptor density.

Objective: The aim of this study was to evaluate the influence of dopaminergic cell loss, induced by injection of 6-hydroxydopamine, on the effects exerted by cannabinoid agonists on neuron activity in the subthalamic nucleus (STN) of anesthetized rats.

Results: We have previously shown that Δ(9)-tetrahydrocannabinol (Δ(9)-THC) and anandamide induce both stimulation and inhibition of STN neuron activity and that endocannabinoids mediate tonic control of STN activity. Here, we show that in intact rats, the cannabinoid agonist WIN 55,212-2 stimulated all recorded STN neurons. Conversely, after dopaminergic depletion, WIN 55,212-2, Δ(9)-THC, or anandamide inhibited the STN firing rate without altering its discharge pattern, and stimulatory effects were not observed. Moreover, anandamide exerted a more intense inhibitory effect in lesioned rats in comparison to control rats.

Conclusions: Cannabinoids induce different effects on the STN depending on the integrity of the nigrostriatal pathway. These findings advance our understanding of the role of cannabinoids in diseases involving dopamine deficits.

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Histological verification of the recording site in the subthalamic nucleus (STN). a Schematic illustration of the recording location of STN neurons. Image modified from Paxinos and Watson (1986), with permission from Elsevier. b Pontamine Sky Blue dots in Neutral Red-stained STN sections at different anatomical levels are homogenously distributed within the nucleus (the examples correspond to recorded neurons in 6-OHDA-lesioned rats and in intact rats in which WIN 55,212-2 was administered). Scale bar, 40 μm
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Fig4: Histological verification of the recording site in the subthalamic nucleus (STN). a Schematic illustration of the recording location of STN neurons. Image modified from Paxinos and Watson (1986), with permission from Elsevier. b Pontamine Sky Blue dots in Neutral Red-stained STN sections at different anatomical levels are homogenously distributed within the nucleus (the examples correspond to recorded neurons in 6-OHDA-lesioned rats and in intact rats in which WIN 55,212-2 was administered). Scale bar, 40 μm

Mentions: After the electrophysiological experiments had been carried out, Pontamine Sky Blue dots were localized in Neutral Red stained STN sections, revealing that all recorded neurons from 6-OHDA-lesioned rats and those that were recorded before and after WIN 55,212-2 administration to intact rats were located quite homogeneously over the entire STN (Fig. 4). Conversely, as we have previously shown (Morera-Herreras et al. 2010a, b), neurons inhibited by Δ9-THC or anandamide are predominantly located in the dorsolateral portion of the rostral STN, whereas stimulated neurons are located in the ventromedial portion of the caudal STN.Fig. 4


Nigrostriatal denervation changes the effect of cannabinoids on subthalamic neuronal activity in rats.

Morera-Herreras T, Ruiz-Ortega JA, Linazasoro G, Ugedo L - Psychopharmacology (Berl.) (2010)

Histological verification of the recording site in the subthalamic nucleus (STN). a Schematic illustration of the recording location of STN neurons. Image modified from Paxinos and Watson (1986), with permission from Elsevier. b Pontamine Sky Blue dots in Neutral Red-stained STN sections at different anatomical levels are homogenously distributed within the nucleus (the examples correspond to recorded neurons in 6-OHDA-lesioned rats and in intact rats in which WIN 55,212-2 was administered). Scale bar, 40 μm
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Related In: Results  -  Collection

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getmorefigures.php?uid=PMC3045509&req=5

Fig4: Histological verification of the recording site in the subthalamic nucleus (STN). a Schematic illustration of the recording location of STN neurons. Image modified from Paxinos and Watson (1986), with permission from Elsevier. b Pontamine Sky Blue dots in Neutral Red-stained STN sections at different anatomical levels are homogenously distributed within the nucleus (the examples correspond to recorded neurons in 6-OHDA-lesioned rats and in intact rats in which WIN 55,212-2 was administered). Scale bar, 40 μm
Mentions: After the electrophysiological experiments had been carried out, Pontamine Sky Blue dots were localized in Neutral Red stained STN sections, revealing that all recorded neurons from 6-OHDA-lesioned rats and those that were recorded before and after WIN 55,212-2 administration to intact rats were located quite homogeneously over the entire STN (Fig. 4). Conversely, as we have previously shown (Morera-Herreras et al. 2010a, b), neurons inhibited by Δ9-THC or anandamide are predominantly located in the dorsolateral portion of the rostral STN, whereas stimulated neurons are located in the ventromedial portion of the caudal STN.Fig. 4

Bottom Line: Conversely, after dopaminergic depletion, WIN 55,212-2, Δ(9)-THC, or anandamide inhibited the STN firing rate without altering its discharge pattern, and stimulatory effects were not observed.Cannabinoids induce different effects on the STN depending on the integrity of the nigrostriatal pathway.These findings advance our understanding of the role of cannabinoids in diseases involving dopamine deficits.

View Article: PubMed Central - PubMed

Affiliation: Department of Pharmacology, Faculty of Medicine, University of the Basque Country, 48940, Leioa, Vizcaya, Spain.

ABSTRACT

Rationale: It is known that dopaminergic cell loss leads to increased endogenous cannabinoid levels and CB1 receptor density.

Objective: The aim of this study was to evaluate the influence of dopaminergic cell loss, induced by injection of 6-hydroxydopamine, on the effects exerted by cannabinoid agonists on neuron activity in the subthalamic nucleus (STN) of anesthetized rats.

Results: We have previously shown that Δ(9)-tetrahydrocannabinol (Δ(9)-THC) and anandamide induce both stimulation and inhibition of STN neuron activity and that endocannabinoids mediate tonic control of STN activity. Here, we show that in intact rats, the cannabinoid agonist WIN 55,212-2 stimulated all recorded STN neurons. Conversely, after dopaminergic depletion, WIN 55,212-2, Δ(9)-THC, or anandamide inhibited the STN firing rate without altering its discharge pattern, and stimulatory effects were not observed. Moreover, anandamide exerted a more intense inhibitory effect in lesioned rats in comparison to control rats.

Conclusions: Cannabinoids induce different effects on the STN depending on the integrity of the nigrostriatal pathway. These findings advance our understanding of the role of cannabinoids in diseases involving dopamine deficits.

Show MeSH