Opposite influences of dopaminergic pathways to the prefrontal cortex or the septum on the dopaminergic transmission in the nucleus accumbens. An in vivo voltammetric study

Louilot, Alain; Moal, Michel Le; Simon, H.

doi:10.1016/0306-4522(89)90331-x

Cited by 200 publications

(71 citation statements)

References 50 publications

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“…It seems then, that the inhibition of cocaine action in the mPFC of the Coc1h animals produced by increased number of D2 receptors, at 20 minutes of withdrawal, could be counteracted by the decreased number of NMDA receptors in this brain area. Since DA levels in the mPFC are inversely related to DA levels in the N.Acc (Carter & Pycock, 1980;Lecesse & Lyness, 1987;Louilot et al, 1989;Pycock et al, 1980a,b), it follows that the net effects of these adaptations on N.Acc DA may be negligible. This hypothesis is consistent with our previous findings (Ben-Shahar et al, 2004) showing similar c-Fos immunoreactive response to cocaine challenge given after 3 days of withdrawal, in the Sal and Coc1h groups.…”

Section: Discussionmentioning

confidence: 99%

Changes in levels of D1, D2, or NMDA receptors during withdrawal from brief or extended daily access to IV cocaine

et al. 2007

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We previously reported that brief (1 hr), but not extended (6 hrs), daily access to cocaine results in a sensitized locomotor response to cocaine and in elevated c-Fos immunoreactivity and DAT binding in the nucleus accumbens (N.Acc) core. In order to better our understanding of the neural adaptations mediating the transition from controlled drug-use to addiction, the current experiments were set to further explore the neural adaptations resulting from these two access conditions. Rats received either brief daily access to saline or cocaine, or brief daily access followed by extended daily access, to cocaine. Subjects were then sacrificed either 20 minutes, or 14 or 60 days, after the last selfadministration session. Samples of the ventral tegmental area (VTA), N.Acc core and shell, dorsal striatum, and medial prefrontal cortex (mPFC) were taken for analysis of D1 ([3H]SCH-23390), D2 ([3H]Spiperone), and NMDA ([3H]MK-801) receptor binding (using the method of receptor autoradiography). At 20 minutes into withdrawal D2 receptors were elevated and NMDA receptors were reduced in the mPFC of the brief access animals while D1 receptors were elevated in the N.Acc shell of the extended access animals, compared to saline controls. D2 receptors were reduced in the N.Acc shell of the brief access animals compared to saline controls after 14 days, and compared to extended access animals after 60 days of withdrawal. In summary, extended access to cocaine resulted in only transient changes in D1 receptors binding. These results suggest that the development of compulsive drug use is largely unrelated to changes in total binding of D2 or NMDA receptors.

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Section: Discussionmentioning

confidence: 99%

Changes in levels of D1, D2, or NMDA receptors during withdrawal from brief or extended daily access to IV cocaine

et al. 2007

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“…32,33 This attenuation would be predicted to reduce the behavioral response to acute amphetamine. Indeed, when we measured basal tissue concentrations of DA and its metabolites in adult dcc and wild-type mice, we found a dramatic increase in DA, DOPAC and HVA concentrations in the mPFC of dcc heterozygotes.…”

Section: Discussionmentioning

confidence: 99%

Netrin receptor deficient mice exhibit functional reorganization of dopaminergic systems and do not sensitize to amphetamine

et al. 2004

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Netrins are guidance cues that play a fundamental role in organizing the developing brain. The netrin receptor, DCC (deleted in colorectal cancer), is highly expressed by dopaminergic (DA) neurons. DCC may therefore participate in the organization of DA circuitry during development and also influence DA function in the adult. Here we show that adult dcc heterozygous mice exhibit a blunted behavioral response to the indirect DA agonist amphetamine and do not develop sensitization to its effects when treated repeatedly. These behavioral alterations are associated with profound changes in DA function. In the medial prefrontal cortex, dcc heterozygotes exhibit increased tyrosine hydroxylase (TH) protein levels and dramatic increases in basal concentrations of DA and DA metabolites. In contrast, in the nucleus accumbens, dcc heterozygotes show no changes in either TH or DA levels, but exhibit decreased concentrations of DA metabolites, suggesting reduced DA activity. In addition, dcc heterozygous mice exhibit a small, but significant reduction in total number of TH-positive neurons in midbrain DA cell body regions. These results demonstrate for the first time that alterations in dcc expression lead to selective changes in DA function and, in turn, to differences in DA-related behaviors in adulthood. These findings raise the possibility that changes in dcc function early in life are implicated in the development of DA dysregulation observed in certain psychiatric disorders, such as schizophrenia, or following chronic use of drugs of abuse. Keywords: axon guidance; DCC; prefrontal cortex; schizophrenia; drug abuse; psychostimulant drugs Repeated exposure to stimulant drugs, such as amphetamine, leads to the development of increased sensitivity to the behavioral-activating effects of these drugs. This phenomenon, known as behavioral sensitization, is long-lasting and is accompanied by enhanced stimulant-induced dopamine (DA) release in the nucleus accumbens (NAcc). 1,2 Individual differences in susceptibility to the effects of stimulants on behavior and on the release of DA have been demonstrated in both humans and adult laboratory animals. [3][4][5][6][7][8] Although the processes that lead to differences in vulnerability to stimulant drugs remain to be elucidated, evidence indicates that both genetic factors 9 and exposure to environmental insults early in life are involved. 10 Perinatal insults can result in sensitized behavioral and mesolimbic DA responses of adult rats to an acute injection of amphetamine. 11 Similarly, lesions of forebrain structures made in neonatal rats lead to enhanced behavioral responses to amphetamine in adult animals. 5,12 These findings suggest that anomalies in the development and organization of DA circuitry contribute to subsequent functional and behavioral abnormalities in the adult. However, little is known about the molecular mechanisms that regulate the development of DA systems.Netrins are a family of secreted proteins that play a fundamental role in the organization of the develop...

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“…A brief, transient increase in dopamine release in both nucleus accumbens shell and prefrontal cortex accompanies entry into a novel environment (Rebec et al, 1997a, b;Rebec, 1998). Increased dopamine release in medial prefrontal cortex generally results in decreased dopamine activity in nucleus accumbens, however (Louilot et al, 1989;Jaskiw et al, 1991;Kolachana et al, 1995;Tzschentke, 2001), and thus while the ventral tegmental-nucleus accumbenspallidal circuit plays a critical role in modulation of locomotion response to both novelty and amphetaminestimulated locomotion (Hooks and Kalivas, 1995), the role of medial prefrontal cortex in these different behavioral measures is likely different. Thus, differences in normalization by risperidone of these two behaviors could reflect differences in the relative importance of cortical and perhaps thalamic inputs to the ventral tegmental-nucleus accumbens-pallidal loop in the regulation of these two different locomotor responses.…”

Section: Discussionmentioning

confidence: 99%

Risperidone Pretreatment Prevents Elevated Locomotor Activity Following Neonatal Hippocampal Lesions

Richtand

Taylor

Welge

et al. 2005

Neuropsychopharmacol

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Long-standing behavioral abnormalities emerge after puberty in rats following neonatal hippocampal lesion, providing a developmental model of abnormal rat behavior that may have predictive validity in identifying compounds effective in treating symptoms of schizophrenia. We sought to test the predictive validity of the neonatal hippocampal lesion model in identifying preventive treatment for first-episode psychosis. We determined the effect of risperidone, recently studied for prevention of first-episode psychosis, on the development of elevated locomotor activity following neonatal hippocampal lesions. Rat pups received hippocampal or sham lesions on postnatal day 7, followed by treatment with risperidone or vehicle from postnatal days 35 to 56. Locomotor activity in response to novelty, amphetamine, and nocturnal locomotion were determined on postnatal day 57. Low-dose risperidone (45 mg/kg) pretreatment prevented elevated locomotor activity in some, but not all, of the behavioral tasks following neonatal hippocampal lesions. In contrast, higher risperidone pretreatment was less effective in preventing elevated locomotor activity following neonatal hippocampal lesions. Because low risperidone dosages were also found to be effective in preventing first-episode psychosis in human studies, these data support the predictive validity of the hippocampal lesion model in identifying medications for prevention of first-episode psychosis. Additionally, these data support the use of low-dose risperidone in psychosis prevention, and suggest the possibility that higher risperidone doses could be less effective in this application.

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Opposite influences of dopaminergic pathways to the prefrontal cortex or the septum on the dopaminergic transmission in the nucleus accumbens. An in vivo voltammetric study

Cited by 200 publications

References 50 publications

Changes in levels of D1, D2, or NMDA receptors during withdrawal from brief or extended daily access to IV cocaine

Changes in levels of D1, D2, or NMDA receptors during withdrawal from brief or extended daily access to IV cocaine

Netrin receptor deficient mice exhibit functional reorganization of dopaminergic systems and do not sensitize to amphetamine

Risperidone Pretreatment Prevents Elevated Locomotor Activity Following Neonatal Hippocampal Lesions

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