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J Glowinski

Publications and source records attributed to J Glowinski.

At least 55 records · Page 3Linked to original sources
PubMed1999

Role of arachidonic acid in the regulation of the NMDA-evoked release of acetylcholine in striatal compartments.

The role of endogenously released arachidonic acid in the control of the NMDA (50 microM)-evoked release of [3H]-acetylcholine previously formed from [3H]-choline was investigated in striosome-enriched areas and in the matrix of the rat striatum using a microsuperfusion procedure in vitro. Experiments were performed with either mepacrine (0.2 microM) or bovine serum albumin (BSA, 0.02%) which inhibits phospholipase A2 activity or binds endogenously released arachidonic acid, respectively. Both treatments similarly reduce the NMDA-evoked release of [3H]-acetylcholine, this effect being more pronounced in striosomes than in the matrix. These reductions result from a facilitation of dopamine release, since they were not observed in the presence of (-)sulpiride, the D2 dopamine receptor antagonist. Moreover, the superfusion with BSA was shown to enhance the release of [3H]-dopamine (formed from [3H]-tyrosine), this effect being of larger amplitude in striosomes than in the matrix. In control conditions, due to the blockade of the presynaptic inhibitory effect of GABA on dopamine release, bicuculline (GABA(A) receptor antagonist) reduces the NMDA-evoked release of [3H]-acetylcholine in both striatal compartments. Bicuculline was no longer effective following superfusions with either mepacrine or BSA, suggesting that these treatments eliminate the GABAergic presynaptic inhibitory control on dopamine transmission and thus lead to the dopamine-mediated inhibition of [3H]-acetylcholine release. These results indicate that arachidonic acid endogenously formed under weak stimulation of NMDA receptors contributes to the regulation of the evoked release of [3H]-acetylcholine by facilitating GABAergic transmission and that this process is more important in striosomes than in the matrix.

Acetylcholine↗
PubMed1999

Pharmacological characterization of tachykinin septide-sensitive binding sites in the rat submaxillary gland.

Binding studies have shown that [125I]NKA is a selective ligand of tachykinin septide-sensitive binding sites from membranes of the rat submaxillary gland. Indeed, this ligand bound with high affinity to a single population of sites. In addition, competition studies indicated that natural tachykinins and tachykinin-related compounds had a similar affinity for these sites than for those labeled with [3H]ALIE-124, a selective ligand of septide-sensitive binding sites. Moreover, selective tachykinin NK2, or NK3 agonists or antagonists exhibited weak or no affinity for [125I]NKA binding sites. As indicated by Ki values of several compounds, the pharmacological characteristics of the septide-sensitive binding sites (labeled with [125I]NKA) largely differ from those of classic NK1 binding sites, as determined on crude synaptosomes from the rat brain using [125I]Bolton-Hunter substance P (SP) as ligand. Indeed, several tachykinins including neurokinin A (NKA), neuropeptide K (NPK), neuropeptide gamma (NKgamma), and neurokinin B, as well as some SP and NKA analogues or C-terminal fragments such as septide, ALIE-124, SP(6-11), NKA(4-10), which have a weak affinity for classic tachykinin NK1 binding sites exhibited a high affinity for the septide-sensitive binding sites. In contrast, SP, classic selective NK1 agonists, and antagonists had a high affinity for both types of binding sites. The presence of a large population of tachykinin septide-sensitive binding sites in the rat submaxillary gland may thus explain why NPK and NPgamma induce salivary secretion and may potentiate the SP-evoked response in spite of the absence of tachykinin NK2 receptors in this tissue.

Animals↗
PubMed1999

Anandamide and WIN 55212-2 inhibit cyclic AMP formation through G-protein-coupled receptors distinct from CB1 cannabinoid receptors in cultured astrocytes.

The effects of anandamide and the cannabinoid receptor agonists WIN 55212-2 and CP 55940 on the evoked formation of cyclic AMP were compared in cultured neurons and astrocytes from the cerebral cortex and striatum of mouse embryos. The three compounds inhibited the isoproterenol-induced accumulation of cyclic AMP in neuronal cells, and these responses were blocked by the selective CB1 receptor antagonist SR 141716A. The three agonists were more potent in cortical than striatal neurons. Interestingly, WIN 55212-2, CP 55940 and anandamide also inhibited the isoproterenol-evoked accumulation of cyclic AMP in astrocytes but, in contrast to WIN 55212-2 and CP 55940, anandamide was much more potent in striatal than cortical astrocytes. Inhibition was prevented by pertussis toxin pretreatment, but not blocked by SR 141716A. Therefore, G-protein-coupled receptors, distinct from CB1 receptors, are involved in these astrocytic responses. Moreover, specific binding sites for [3H]-SR 141716A were found in neurons but not astrocytes. Furthermore, using a polyclonal CB1 receptor antibody, staining was observed in striatal and cortical neurons, but not in striatal and cortical astrocytes. Taken together, these results suggest that glial cells possess G-protein-coupled receptors activated by cannabinoids distinct from the neuronal CB1 receptor, and that glial cells responses must be taken into account when assessing central effects of cannabinoids.

Adrenergic beta-Agonists↗
PubMed1999

Contribution of endogenously formed arachidonic acid in the presynaptic facilitatory effects of NMDA and carbachol on dopamine release in the mouse striatum.

Arachidonic acid stimulated the release of [3H]-dopamine from striatal microdiscs in a concentration-dependent and partially calcium-dependent manner. Inhibitors of cytosolic and membrane-bound phospholipase A2 were used to determine whether endogenously formed arachidonic acid also contributes to the release of [3H]-DA (previously taken up in tissues or endogenously synthesized from [3H]-tyrosine) evoked by N-methyl-d-aspartate (NMDA) and carbachol alone or in combination. In the presence of magnesium, carbachol was found to remove the magnesium block of NMDA receptors and to facilitate the NMDA-evoked release of [3H]-DA from striatal microdiscs and synaptosomes. In addition, in the absence of magnesium, synergistic responses were induced by both agonists on microdiscs but not on synaptosomes. Responses induced by NMDA, carbachol or both agonists on microdiscs were reduced by phospholipase A2 inhibitors, the most striking effects being observed with mepacrine. Mepacrine was also shown to reduce the oxotremorine, but neither the nicotine- nor the potassium-evoked release of [3H]-DA. Tetrodotoxin decreased the release of [3H]-DA evoked by the co-application of NMDA and carbachol on microdiscs, but mepacrine still decreased this tetrodotoxin-resistant response. Similarly, mepacrine still decreased the release of [3H]-DA evoked by NMDA and carbachol on synaptosomes. Altogether, these results indicate that arachidonic acid which is formed in striatal neurons, and to a lesser extent in DA fibres, under stimulation of NMDA and muscarinic receptors, partially contributes to the presynaptic facilitation of DA release evoked by NMDA and carbachol.

Animals↗
PubMed1999

Pyruvate and lactate protect striatal neurons against N-methyl-D-aspartate-induced neurotoxicity.

A sustained release of glutamate contributes to neuronal loss during cerebral ischaemia. Using cultured mouse striatal neurons, we observed that glucose deprivation, which occurs in this pathological process, enhanced the N-Methyl-D-aspartate (NMDA)- or alpha-amino-3-hydroxy-5-methylisoxazole-4-propionate (AMPA)-induced neurotoxicity. The end products of glycolysis, lactate and pyruvate, strongly protected neurons from these neurotoxic effects. The neuroprotective effect of pyruvate (which is more prominent in the absence of glucose) was not related to its ability to react with H2O2 by a decarboxylation process. Pyruvate and L-lactate strongly counteracted the deep decrease in the neuronal ATP content induced by NMDA, indicating that they might protect striatal neurons by rescuing cellular energy charge. Addition of MK-801 after the NMDA withdrawal completely protected neurons, suggesting that NMDA neurotoxicity resulted from a delayed NMDA receptor activation probably linked to a delayed release of an endogenous agonist in the extracellular medium. The strong accumulation of extracellular glutamate which was found in both sham and NMDA-treated cultures was markedly decreased by pyruvate. Thus, pyruvate might also exert its protecting activity by decreasing the delayed accumulation of glutamate which seemed to be neurotoxic only after a preexposure of neurons to NMDA.

Adenosine Triphosphate↗
PubMed1999

Increase in external glutamate and NMDA receptor activation contribute to H2O2-induced neuronal apoptosis.

The present study aims to investigate the role of extracellular glutamate and NMDA receptor stimulation in the neuronal death induced by a transient exposure to H2O2 of cultured neurons originating from mouse cerebral cortex. Most of the neuronal loss following a transient exposure to H2O2 of cortical neurons results from an apoptotic process involving a secondary stimulation of NMDA receptors, which occurs after H2O2 washout. Indeed, (a) the neurotoxic effect of H2O2 was strongly reduced by antagonists of NMDA receptors, (b) the neurotoxic effect of H2O2 was enhanced in the absence of Mg2+, (c) the protective effect of MK-801 progressively decayed when it was applied with increasing delay time after H2O2 exposure, and (d), finally, the extracellular concentration of glutamate was increased after H2O2 exposure. The major part of H2O2-induced neurotoxicity is mediated by the formation of hydroxyl radicals, which might be involved in (a) the delayed accumulation of extracellular glutamate and NMDA receptor activation and (b) the poly(ADP-ribose) polymerase activation and the related NAD content decrease. The combination of these two mechanisms could lead to both an increase in ATP consumption and a decrease of ATP synthesis. The resulting large decrease in ATP content might be finally responsible for the neuronal death.

Adenosine Triphosphate↗
PubMed1999

Spinal tuberculosis in adults. A study of 103 cases in a developed country, 1980-1994.

Spinal tuberculosis (TB) accounts for about 2% of all cases of TB. New methods of diagnosis such as magnetic resonance imaging (MRI) or percutaneous needle biopsy have emerged. Two distinct patterns of spinal TB can be identified, the classic form, called spondylodiscitis (SPD) in this article, and an increasingly common atypical form characterized by spondylitis without disk involvement (SPwD). We conducted a retrospective study of patients with spinal TB managed in the area of Paris, France, between 1980 and 1994 with the goal of defining the characteristics of spinal TB and comparing SPD to SPwD. The 103 consecutive patients included in our study had TB confirmed by bacteriologic and/or histologic studies of specimens from spinal or paraspinal lesions (93 patients) or from extraspinal skeletal lesions (10 patients). Sixty-eight percent of patients were foreign-born subjects from developing countries. None of our patients was HIV-positive. SPD accounted for 48% of cases and SPwD for 52%. Patients with SPwD were younger and more likely to be foreign-born and to have multiple skeletal TB lesions. Neurologic manifestations were observed in 50% of patients, with no differences between the SPD and SPwD groups. Of the 44 patients investigated by MRI, 6 had normal plain radiographs; MRI was consistently positive and demonstrated epidural involvement in 77% of cases. Bacteriologic and histologic yields were similar for surgical biopsy (n = 16) and for percutaneous needle aspiration and/or biopsy (n = 77). Cultures for Mycobacterium tuberculosis were positive in 83% of patients, and no strains were resistant to rifampin. Median duration of antituberculous chemotherapy was 14 months. Surgical treatment was performed in 24% of patients. There were 2 TB-related deaths. Our data suggest that SPwD may now be the most common pattern of spinal TB in foreign-born subjects in industrialized countries. The reasons for this remain to be elucidated.

Adolescent↗
PubMed1999

Nonsurgical treatment of osteoarticular tuberculosis. A retrospective study in 143 adults.

OBJECTIVE AND METHODS: Data are sparse on nonsurgical treatments currently used for osteoarticular tuberculosis in industrialized countries. We conducted a multicenter retrospective study in the Paris urban area, France, in 206 cases of osteoarticular tuberculosis documented by examination of a local specimen. This article reports our findings in the 143 patients who were followed up at least until treatment completion. RESULTS: Mean follow-up after treatment completion was 16 months. Seventy-five (52%) patients had spondylitis and 68 (48%) did not. The number of antituberculous agents used during the initial treatment phase was four in 65% of cases and three in 35%. In the spondylitis subgroup, mean (+/- SD) antibiotic therapy duration was 14.7 +/- 3.4 months, and 25% of patients required surgery; 3% of patients died, 1% suffered a relapse, and 96% achieved a full recovery with no relapse. In the nonspondylitis subgroup, mean antibiotic therapy duration was 13 +/- 3 months and 29% of patients required surgery. The only HIV-positive patient had osteitis of the calcaneus with a relapse that led to discovery of secondary rifampin resistance. CONCLUSION: Based on our findings and on data from the literature, we believe that 12 months is a reasonable duration for antituberculous therapy in osteoarticular tuberculosis, including tuberculous spondylitis.

Adolescent↗
PubMed1999

Lymph node tuberculosis in the suburbs of Paris: 59 cases in adults not infected by the human immunodeficiency virus.

We report 59 cases of lymph node tuberculosis in adults not infected by the human immunodeficiency virus (HIV), observed over a period of 5 years in the North Eastern suburbs of Paris. There were 31 women and 28 men; 84.7% were aged under 44 years; 69.5% were not French, and 78% had exclusive lymph node tuberculosis. A superficial distribution was found in 52 cases and a deep pattern in 17 cases. Cervical and supraclavicular lymphadenopathies were the most common (64.4%). General symptoms were present in 63% of cases. The diagnosis was established by fine needle aspiration in 10 cases and by biopsy in 36 cases. Three cases of primary resistance to anti-tuberculosis therapy were described. Lymph node tuberculosis is still present in the Paris region, independently of HIV infection, probably due to poor social conditions.

Adolescent↗
PubMed1998

Relationships between the prefrontal cortex and the basal ganglia in the rat: physiology of the corticosubthalamic circuits.

The prelimbic-medial orbital areas (PL/MO) of the prefrontal cortex are connected to the medial part of the subthalamic nucleus (STN) through a direct projection and an indirect circuit that involves the core of the nucleus accumbens (NAcc) and the ventral pallidum (VP). In the present study, the influence of the PL/MO on the discharge of STN cells has been characterized. The major pattern of the responses observed after stimulation of PL/MO consisted of two excitatory peaks often separated by a brief inhibitory period. The early excitation was most likely to be caused by the activation of direct cortical inputs because its latency matches the conduction time of the prefrontal STN projections. The late excitation resulted from the activation of the indirect PL/MO-STN pathway that operates through a disinhibitory process. Indeed, the late excitation was no longer observed after acute blockade of the glutamatergic corticostriatal transmission by CNQX application into the NAcc. A similar effect was obtained after the blockade of the GABAergic striatopallidal transmission by bicuculline application into the VP. Finally, the brief inhibition that followed the early excitation was likely to result from the activation of a feedback inhibitory loop through VP because this inhibition was no longer observed after the blockade of STN inputs by CNQX application into the VP. This study further indicates the implication of STN in prefrontal basal ganglia circuits and underlines that in addition to a direct excitatory input, medial STN receives an indirect excitatory influence from PL/MO through an NAcc-VP-STN disinhibitory circuit.

6-Cyano-7-nitroquinoxaline-2,3-dione↗
PubMed1998

Gap junctional communication and pharmacological heterogeneity in astrocytes cultured from the rat striatum.

Indo-1 and fluo-3 imaging techniques were used to investigate the role of gap junctions in the changes in cytosolic calcium concentrations ([Ca2+]i) induced by several receptor agonists. Subpopulations of confluent cultured astrocytes from the rat striatum were superfused with submaximal concentrations of endothelin-1 (Et1) and the alpha 1-adrenergic and muscarinic receptor agonists, methoxamine and carbachol, respectively. 2. Combined binding and autoradiographic studies indicated that all striatal astrocytes possess binding sites for Et1. In contrast, alpha 1-adrenergic and muscarinic binding sites were found to be heterogeneously distributed. In agreement with these findings, Et1 induced fast calcium responses in all cells while only subsets of striatal astrocytes responded to the application of methoxamine or carbachol. 3. Halothane, heptanol and octanol, which are commonly used as gap junction inhibitors, drastically reduced the amplitude of Et1-induced calcium responses. In contrast, 18-alpha-glycyrrhetinic acid (alpha GA) used at a concentration known to block gap junction permeability in astrocytes had no significant effect on the amplitude of these calcium responses. 4. As demonstrated by quantitative and topological analysis, Et1 application similarly increased [Ca2+]i levels in all astrocytes in both the absence and presence of alpha GA. 5. In control conditions, subpopulations of cells responding to methoxamine or carbachol exhibited two main types of calcium responses which differed in their shape and kinetic characteristics. In the presence of alpha GA the number of cells responding to these receptor agonists was significantly reduced. Indeed, responses characterized by their long latency, slow rise time and weak amplitude disappeared in the presence of alpha GA while responses with short latency and fast rise time were preserved. 6. These results indicate that permeable gap junction channels tend to attenuate the pharmacological and functional heterogeneity of populations of astrocytes, while their inhibition restricts calcium responses in astrocytes expressing high densities of transmitter receptors coupled to phospholipase C.

Animals↗
PubMed1998

Lack of autoreceptor-mediated inhibitory control of dopamine release in striatal synaptosomes of D2 receptor-deficient mice.

Mouse purified striatal synaptosomes were used to study the release of newly synthesised [3H]-dopamine ([3H]-DA) or of previously taken up [3H]-DA. Quinpirole (QP, 10 microM), a D2/D3 dopaminergic agonist, was found to reduce the release of newly synthesised [3H]-DA with a larger amplitude when 4-aminopyridine (100 microM) instead than veratridine (1 microM) or potassium (25 mM) was used to evoke DA release. Among the different D2/D3 dopaminergic agonists tested R(-)-propylnorapomorphine (NPA) and quinpirole were the most potent. These compounds reduced, in a concentration-dependent manner, the 4-aminopyridine-evoked release of [3H]-DA previously taken up by synaptosomes (50% maximal inhibition). In contrast, the D3 agonist PD-128,907 had little effect even when used at 100 nM. The QP (100 nM)-induced response was completely antagonised by sulpiride (1 microM). Strikingly, the NPA (100 nM) and PD-128,907 (100 nM)-evoked responses were completely suppressed in D2 receptor-deficient mice. This data strongly suggest that only D2 but not D3 receptors are involved in the autoreceptor-mediated inhibition of the evoked release of [3H]-DA. Interestingly, while amphetamine-induced release of [3H]-DA was not modified, a slight reduction of [3H]-DA efflux induced by the dopamine (DA) uptake inhibitor cocaine was observed in D2 receptor-deficient mice.

4-Aminopyridine↗
PubMed1998

Importance of the noradrenaline-dopamine coupling in the locomotor activating effects of D-amphetamine.

The locomotor hyperactivity induced by systemic or local (nucleus accumbens) D-amphetamine injections can be blocked by systemic or local (prefrontal cortex) injections of prazosin, an alpha1-adrenergic antagonist (Blance et al., 1994). Microdialysis studies performed on freely moving animals indicated that prazosin (0.5 mg/kg, i.p.) does not modify the increase in the extracellular dopamine (DA) levels in the nucleus accumbens that are induced by D-amphetamine (2.0 mg/kg, i.p.), but it inhibits the D-amphetamine-induced locomotor hyperactivity (-63%, p < 0.0001). No behavioral activation occurred after the bilateral local perfusion of 3 microM D-amphetamine in the nucleus accumbens, although it led to a fivefold increase in extracellular DA levels. This increase in extracellular DA levels was not affected by prazosin (0.5 mg/kg, i.p.). When an intraperitoneal injection of D-amphetamine (0.5 mg/kg) was superimposed to the continuous local perfusion of 3 microM D-amphetamine, it induced a 64% increase in the extracellular DA levels in the nucleus accumbens, and this response was associated with simultaneous behavioral activation. Both the increases in extracellular DA levels and in locomotor activity were completely blocked by a pretreatment with prazosin, injected either systemically (0.5 mg/kg, i.p.) or locally and bilaterally into the prefrontal cortex (500 pmol/side). Complementary experiments indicated that the focal application of D-amphetamine requires at least a 4.8-fold higher increase in DA output compared with systemic D-amphetamine for the behavioral effects to be elicited. Altogether, these results suggest that locomotor activating effects of D-amphetamine are caused by the stimulation of cortical alpha1-adrenergic receptors by noradrenaline, which increases the release of a functional part of subcortical DA.

Adrenergic Agents↗
PubMed1998

A 21-kDa polypeptide belonging to a new family of proteins is expressed in the Golgi apparatus of neural and germ cells.

We have isolated a full-length murine clone corresponding to the rat neuronal p1A75 partial cDNA (Sutcliffe, J. G., Milner, R. J., Shinnick, T. M., and Bloom, F. E. (1983) Cell 33, 671-682). It encodes a 185-residue polypeptide that displays 56% identity with p19, a protein selectively expressed in the Golgi apparatus of neural cells (Sabéran-Djoneidi, D., Marey-Semper, I., Picart, R., Studler, J.-M., Tougard, C., Glowinski, J., and Lévi-Strauss, M. (1995) J. Biol. Chem. 270, 1888-1893). An antibody directed against the recombinant polypeptide allowed us to demonstrate the existence of the natural 21-kDa protein (p21) in brain and its prominent juxtanuclear Golgi-like localization in cultured neurons. Ultrastructural observation of cultured neurons and analysis of transfected COS cells revealed a specific labeling of the Golgi apparatus, suggesting, as for p19, the presence of a Golgi targeting signal in its primary sequence. Surprisingly, p21, which is much more strongly expressed in the olfactory epithelium than p19, is also present in the Golgi complex of spermatocytes and in the flagellar middle piece of late spermatids.

Amino Acid Sequence↗
PubMed1998

Identification of CSF-1 as a brain macrophage migratory activity produced by astrocytes.

Intraparenchymal migration of macrophages occurs in the CNS during development or as a consequence of tissue injuries. In the present study, we have shown, by using an in vitro chemotaxis assay, that cultured rat astrocytes obtained from the developing cerebral cortex and striatum produce soluble factors, which attract purified brain macrophages. The effect of astrocyte-derived factors on macrophages was strongly reduced in the presence of antibodies neutralizing colony-stimulating factor 1 (CSF-1, also called M-CSF), and recombinant CSF-1 was found to act as a chemotactic agent on brain macrophages. Synthesis of CSF-1 by cultured astrocytes was confirmed by northern detection of CSF-1 transcripts. In contrast, the CSF-1 gene was not expressed by cultured neurons from the cerebral cortex and striatum or by the brain macrophage population responsive to CSF-1 gradient. ELISA detection of CSF-1 in tissue extracts revealed the occurrence of this cytokine in the rat cerebral cortex during postnatal development and in adults. Altogether, our results demonstrate that astrocytes, through CSF-1 secretion, can trigger the polarized migration of brain macrophages and suggest a new mechanism which could regulate the locomotion of these cells in the cerebral cortex during ontogenesis or following lesions.

Animals↗
PubMed1998

Prefrontal cortex-basal ganglia circuits in the rat: involvement of ventral pallidum and subthalamic nucleus.

The core of the nucleus accumbens (NAcc core) is the principal input structure to the basal ganglia circuitry for the prelimbic and medial orbital areas (PL/MO) of the prefrontal cortex. As is now well recognized in the rat, the main basal ganglia output of this prefrontal channel is the dorsomedial part of the substantia nigra pars reticulata (SNR) and not the ventral pallidum as previously suggested. There is evidence suggesting that the ventral pallidum is rather involved with the subthalamic nucleus (STN) in an indirect NAcc-SNR pathway. Indeed, we have recently shown that the NAcc core sends an inhibitory input to the lateral ventral pallidum (VPl), which projects to the medial STN. In the present study, we injected biocytin into the medial STN, at a site where neurons presented an inhibitory response to VPl stimulation. This produced anterogradely labelled fibres in the medial SNR and in the VPl. Furthermore, the stimulation of the VPl induced an inhibition in a majority of the STN cells identified, by the antidromic activation method, as projecting to SNR (76.6%) and/or back to the VPl (72.7%). In conclusion, these data further demonstrate the existence of an indirect striato-nigral pathway in the PL/MO channel and indicate that VPl is involved in an inhibitory feedback circuit, which modulates the discharge of medial STN. These results indicate that the medial STN is implicated in the limbic/cognitive functions of the basal ganglia.

Animals↗
PubMed1998

Alpha1-adrenergic, D1, and D2 receptors interactions in the prefrontal cortex: implications for the modality of action of different types of neuroleptics.

The activation of rat mesocortical dopaminergic (DA) neurons evoked by the electrical stimulation of the ventral tegmental area (VTA) induces a marked inhibition of the spontaneous activity of prefrontocortical cells. In the present study, it was first shown that systemic administration of either clozapine (a mixed antagonist of D1, D2, and alpha1-adrenergic receptors) (3-5 mg/kg, i.v.), prazosin (an alpha1-adrenergic antagonist) (0.2 mg/kg, i.v.), or sulpiride (a D2 antagonist) (30 mg/kg, i.v.), but not SCH 23390 (a D1 antagonist) (0.2 mg/kg, i.v.), reversed this cortical inhibition. Second, it was found that following the systemic administration of prazosin, the VTA-induced cortical inhibition reappeared when either SCH 23390 or sulpiride was applied by iontophoresis into the prefrontal cortex. Third, it was seen that, whereas haloperidol (0.2 mg/kg, i.v.), a D2 antagonist which also blocks alpha1-adrenergic receptors, failed to reverse the VTA-induced inhibition, the systemic administration of haloperidol plus SCH 23390 (0.2 mg/kg, i.v.) blocked this inhibition. Finally, it was verified that the cortical inhibitions obtained following treatments with either "prazosin plus sulpiride" or "prazosin plus SCH 23390" were blocked by a superimposed administration of either SCH 23390 or sulpiride, respectively. These data indicate that complex interactions between cortical D2, D1, and alpha1-adrenergic receptors are involved in the regulation of the activity of prefrontocortical cells innervated by the VTA neurons. They confirm that the physiological stimulation of cortical alpha1-adrenergic receptors hampers the functional activity of cortical D1 receptors and suggest that the stimulations of cortical D1 and D2 receptors exert mutual inhibition on each other's transmission.

Animals↗