PubMed · 14142739
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W A HAWKE, D A MCGREAL. 1964. TRANQUILIZERS.. https://doi.org/10.1177/000992286400300402
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The effects of paradoxical sleep deprivation (PSD-48 h) on the conditioned and unconditioned components of behavioural sensitization to amphetamine (two injections of 2.0 mg/kg, separated by 7 days) were studied using locomotion frequency of mice observed in an open-field as experimental parameter. Behavioural sensitization only occurred in PS deprived mice that were exposed to the open-field after the first amphetamine injection. The possible involvement of PSD in the development of a Pavlovian association between the stimulant effect of amphetamine and environmental as well as interoceptive drug cues is discussed.
Metabotropic glutamate receptor 5 (mGluR5) is densely expressed in medium-sized spiny projection neurons of the rat striatum. Activation of mGluR5 increases intracellular Ca2+, resulting in Ca(2+)-dependent cellular responses. Acute administration of the psychostimulant amphetamine (AMPH) induces immediate early gene (IEG) expression in the striatum, which is considered an important molecular event for the development of striatal neuroplasticity related to the addictive properties of drugs of abuse. This study investigated the role of mGluR5 in the mediation of IEG expression in the rat striatum induced by a single dose of AMPH (4 mg/kg, i.p.) in vivo. We found that systemic administration of the mGluR5-selective antagonist 2-methyl-6-(phenylethynyl) pyridine hydrochloride (MPEP) at a dose of 10 mg/kg, i.p. reduced AMPH-stimulated c-fos mRNA levels in the dorsal (caudoputamen) and ventral (nucleus accumbens) striatum as revealed by quantitative in situ hybridization. Similar results were observed in the three areas of cerebral cortex (cingulate, sensory, and piriform cortex). In contrast to c-fos mRNAs, AMPH-stimulated mRNA expression of another IEG, zif/268, was not significantly altered by the blockade of mGluR5 with MPEP in the entire striatum and the three areas of cortex. Treatment with MPEP alone had no effect on basal levels of c-fos and zif/268 mRNAs in the striatal and cortical areas. These results indicate that an mGluR5-dependent mechanism selectively contributes to c-fos expression in the striatum and cortex in response to acute exposure to AMPH.
Pregnant rats subjected to very mild stress give birth to pups who, when examined as adults, exhibited behavioral and anatomical anomalies that resemble some aspects of schizophrenia. The nucleus accumbens (NAcc) is reduced in volume by 20.7 +/- 3.4% (p = 0.003) in pups born to mothers who were stressed during pregnancy by injections of either saline or amphetamine in saline. The total number of cells is decreased in proportion to the reduction in volume, so the volume cell density of the NAcc is not changed with treatment. The affected volume is localized in the ventral rostral area of the NAcc. Both males and females are affected, but males are slightly more sensitive to the challenge to the mother. Rats born to mothers stressed in mid-pregnancy appear to provide useful parallels to the fetal developmental hypothesis of schizophrenia and to the brain abnormalities seen in this disease.