32 research outputs found
Place preference induced by nucleus accumbens amphetamine is impaired by local blockade of Group II metabotropic glutamate receptors in rats
BACKGROUND: The nucleus accumbens (NAc) plays a critical role in amphetamine-produced conditioned place preference (CPP). In previous studies, NAc basal and amphetamine-produced DA transmission was altered by Group II mGluR agents. We tested whether NAc amphetamine CPP depends on Group II mGluR transmission. RESULTS: NAc injections (0.5 μl/side) of the Group II mGluR antagonist (2 S)- a-ethylglutamic acid (EGLU: 0.01–0.8 μg but not 0.001 μg) impaired CPP. The drug did not block the acute locomotor effect of amphetamine. CONCLUSION: Results suggest that Group II mGluRs may be necessary for the establishment of NAc amphetamine-produced CPP. These receptors may also mediate other forms of reward-related learning dependent on this structure
Transfer of Neuroplasticity from Nucleus Accumbens Core to Shell Is Required for Cocaine Reward
It is well established that cocaine induces an increase of dendritic spines density in some brain regions. However, few studies have addressed the role of this neuroplastic changes in cocaine rewarding effects and have often led to contradictory results. So, we hypothesized that using a rigorous time- and subject-matched protocol would demonstrate the role of this spine increase in cocaine reward. We designed our experiments such as the same animals (rats) were used for spine analysis and behavioral studies. Cocaine rewarding effects were assessed with the conditioned place preference paradigm. Spines densities were measured in the two subdivisions of the nucleus accumbens (NAcc), core and shell. We showed a correlation between the increase of spine density in NAcc core and shell and cocaine rewarding effects. Interestingly, when cocaine was administered in home cages, spine density was increase in NAcc core only. With anisomycin, a protein synthesis inhibitor, injected in the core we blocked spine increase in core and shell and also cocaine rewarding effects. Strikingly, whereas injection of this inhibitor in the shell immediately after conditioning had no effect on neuroplasticity or behavior, its injection 4 hours after conditioning was able to block neuroplasticity in shell only and cocaine-induced place preference. Thus, it clearly appears that the neuronal plasticity in the NAcc core is essential to induce plasticity in the shell, necessary for cocaine reward. Altogether, our data revealed a new mechanism in the NAcc functioning where a neuroplasticity transfer occurred from core to shell
Effects of calpain inhibition on dopaminergic markers and motor function following intrastriatal 6-hydroxydopamine administration in rats.
The neurotoxin 6-hydroxydopamine has been
widely used to model aspects of Parkinson\u2019s disease in rodents,
but the mechanisms underlying toxin-induced dopaminergic
degeneration and functional impairment have not
been fully elucidated. The main aim of the present study was
to assess a possible role for calpains in neurochemical and
behavioral deficits following unilateral infusion of intrastriatal
6-hydroxydopamine in adult rats. Toxin administration
produced a profound dopaminergic denervation, as indicated
by a 90\u201395% reduction in dopamine transporter radiolabeling
measured in the caudate-putamen at 2 weeks post-lesion.
Treatment with 6-hydroxydopamine also resulted in calpain
activation in both caudate-putamen and substantia nigra, as
measured by the appearance of calpain-specific spectrin
breakdown products. Calpain activation peaked at 24 h after
6-hydroxydopamine infusion and remained elevated at later
time points. In contrast, caspase-3-mediated spectrin cleavage
subsided within 48 h in both brain areas. In a subsequent
experiment, calpain inhibition was achieved by intrastriatal
infusion of an adenovirus expressing the endogenous calpain
inhibitor, calpastatin. Calpastatin delivery abolished the
lesion-induced calpain-mediated spectrin cleavage and alleviated
forelimb asymmetries resulting from unilateral intrastriatal
6-hydroxydopamine. Unexpectedly, dopamine transporter
and tyrosine hydroxylase labeling revealed significant
neuroprotection, not in the nigrostriatal pathway but rather in
the ventral tegmental area. These findings support a role for
calpain activation in 6-hydroxydopamine-induced degeneration
of dopaminergic neurons. However, after near-total dopaminergic
depletion, the primary benefit of calpain inhibition
may not occur within the nigrostriatal dopaminergic
pathway itself. \ua9 2009 IBRO. Published by Elsevier Ltd. All
rights reserved.
Key words: calpastatin, caspase, dopamine, 6-hydroxydopamine,
motor, striatum