D3 dopamine receptors interact with dopamine D1 but not D4 receptors in the GABAergic terminals of the SNr of the rat.

The firing rate of substantia nigra reticulata (SNr) neurons is modulated by GABA release from striatonigral and pallidonigral projections. This release is, in turn, modulated by dopamine acting on dopamine D1 receptors at striatonigral terminals and D4 receptors at pallidonigral terminals. In addition, striatal neurons that express D1 receptors also express D3 receptors. In this study we analyzed the possible significance of D3 and D1 receptor colocalization in striatonigral projections. We found that these receptors coprecipitate in SNr synaptosomes suggesting their close association in this structure. D1 agonist SKF 38393 administered alone increased mIPSC frequency in SNr slices and cAMP production in SNr synaptosomes, however, the selective D3 agonist PD 128,907 increased mIPSC frequency and cAMP production only when D1 receptors were concurrently stimulated. The D1 antagonist SCH 23390 blocked completely the effects of the concurrent administration of these agonists while the selective D3 antagonist GR 103691 blocked only the potentiating effects of PD 128,907. These findings further indicate that D1 and D3 receptors are localized in the same structure. The D4 agonist PD 168,077 decreased mIPSCs frequency without changing amplitude, an effect that was blocked by the selective D4 antagonist L 745,870. The effects of D4 receptor stimulation disappeared after lesioning the globus pallidus. D3 agonist PD 128,907 did not reduce mIPSC frequency even in neurons that responded to D4 agonist. In sum, activation of D3 receptors in SNr potentiates the stimulation of transmitter release and cAMP production caused by D1 receptor activation of striatonigral projections while it is without effects in terminals, probably of pallidal origin, that are inhibited by activation of D4 receptors.

Dopamine D4 receptor stimulation in GABAergic projections of the globus pallidus to the reticular thalamic nucleus and the substantia nigra reticulata of the rat decreases locomotor activity.

Dopamine D4 receptors are localized in the GABAergic projections that globus pallidus (GP) neurons send to the reticular nucleus of the thalamus (RTN), the substantia nigra reticulata (SNr) and the subthalamic nucleus (STN). Deficient D4 function in this network could lead to hyperactivity and thus be important in generating some of the symptoms of ADHD (attention deficit hyperactivity disorder), a condition associated with polymorphisms of dopamine D4 receptors. It is then, unexpected that systemic injections of D4 ligands have no significant effects on the motor activity of normal rats. We further examined this issue by microinjecting D4 ligands and psychostimulant drugs in relevant structures. Interstitial dopamine overflow in the RTN was increased by reverse microdialysis of both methylphenidate and methamphetamine. Intranuclear injections in the RTN of methylphenidate, methamphetamine and the selective D4 agonist PD 168,077 reduced motor activity. Intraperitoneal injection of the D4 antagonist L 745,870 blocked the effects of these intranuclear injections. Similarly, intranuclear injections of PD 168,077 in the SNr inhibited motor activity, an effect that was also blocked by intraperitoneal L 745,870. In rats with 6-OHDA induced hemiparkinsonism, intraperitoneal PD 168,077 produced ipsilateral turning behavior that was blocked by L 745,870. Our results suggest that diminished D4 signaling in GP projections could lead to increased traffic through the relay nuclei of the thalamus and hyperactivity. Hence this basal-ganglia-thalamus network may be one of the targets of the beneficial effects that psychostimulant drugs have in disorders associated with D4 receptor abnormalities. This article is part of a Special Issue entitled 'Post-Traumatic Stress Disorder'.

Efectos de la administración central de agonistas GABAérgicos sobre la microestructura de la conducta alimenticia. Estudio experimental en ratas / Response to central administration of GABAergic agents on the microestructure of feeding behaviour. Experimental trial in rats

Debido a la administración de muscimol en el HVM (hipotálamo ventromedial) la ingesta de carbohidratos y la ingesta total se incrementaron; conductualmente este aumento de la ingesta de alimento se caracterizó por el aumento del tiempo total, asociado a un incremento en la duración de los episodios alimentarios. La administración de baclofén en el HVM incrementó la ingesta de carbohidratos y la ingesta total, este aumento se caracterizó por episodios alimentarios menos frecuentes pero más largos. Se confirma que la estimulación de los receptores GABAA y GABAB en el HVM inducen la alimentación y se concluye que el sistema GABAérgico está involucrado en el control de la conducta alimenticia.