On the Role of Enkephalin Cotransmission in the GABAergic Striatal Efferents to the Globus Pallidus

Striatal Preproenkephalin Gene Expression Is Upregulated in Acute but Not Chronic Parkinsonian Monkeys: Implications for the Contribution of the Indirect Striatopallidal Circuit to Parkinsonian Symptomatology

“…mission seems not to be responsible for the generation of symptoms. This has also been suggested to be the case in reserpinized rats (Maneuf et al, 1994) and in M P TP-treated mice (Gudehithlu et al, 1991). Also, the present findings question the functional significance of upregulated GABA /enkephalin transmission in the indirect striatopallidal pathway hypothesized to occur in the current model of basal ganglia f unctional circuitry in parkinsonism.…”

“…directly related to generation of parkinsonian symptoms. Maneuf et al (1994) have suggested that increased enkephalinergic transmission in the striatopallidal circuit could represent an endogenous mechanism attempting to reduce an overactive inhibitory GABAergic input from the striatum. This potential compensatory mechanism may fail in chronic parkinsonian animals.…”

Targeting Group III Metabotropic Glutamate Receptors Produces Complex Behavioral Effects in Rodent Models of Parkinson's Disease

“…Although this comparison only provides indirect evidence, these results suggest that the functional effects of ACPT-I and L-AP4 may be related to a modulation of GABA activity in the GP. In line with this suggestion, intrapallidal injections of picrotoxin or bicuculline induce anti-akinetic effects in various models of PD in rats (Ossowska et al, 1984;Scheel-Kruger, 1984;Herrera-Marschitz and Ungerstedt, 1987;Maneuf et al, 1994;Wisniecki et al, 2003). In contrast, intrapallidal injections of muscimol induce catalepsy (Scheel-Kruger, 1984) and akinesia in the RT task (Amalric and Koob, 1989).…”

Different Mechanisms Underlying the Antiepileptic and Antiparkinsonian Effects of Zonisamide

“…Indeed, depletion of dopaminergic transmission produces overinhibition of pallido-subthalamic GABAergic and disinhibition of subthalamonigral glutamatergic projections in the indirect pathway (DeLong, 1990;Hauber, 1998). Enkephalin is colocalized and acts as cotransmitter with GABA in striatal neurons that project to GP; however, enkephalin reduces the GABAergic inhibition in the indirect pathway via inhibition of GABA release (Maneuf et al, 1994). Based on these effects, the δ opioid receptor and its endogenous agonist enkephalin have been proposed as a suitable target in the symptomatic therapy of Parkinson's disease (Hille et al, 2001;Maneuf et al, 1994).…”

“…Enkephalin is colocalized and acts as cotransmitter with GABA in striatal neurons that project to GP; however, enkephalin reduces the GABAergic inhibition in the indirect pathway via inhibition of GABA release (Maneuf et al, 1994). Based on these effects, the δ opioid receptor and its endogenous agonist enkephalin have been proposed as a suitable target in the symptomatic therapy of Parkinson's disease (Hille et al, 2001;Maneuf et al, 1994). Local administration of antiepileptic-relevant concentrations of ZNS in the striatum increases dopamine release, whereas the use of antiparkinsonian-relevant concentration of ZNS does not affect striatal dopamine release (Yamamura et al, 2009b).…”