Abstract
BackgroundThe aim of the study was to test long-term effects of (+)-methamphetamine (MA) on the dopamine (DA) innervation in limbo-cortical regions of adult gerbils, in order to understand better the repair and neuroplasticity in disturbed limbic networks.MethodsMale gerbils received a single high dose of either MA (25 mg/kg i.p.) or saline on postnatal day 180. On postnatal day 340 the density of immunoreactive DA fibres and calbindin and parvalbumin cells was quantified in the right hemisphere.ResultsNo effects were found in the prefrontal cortex, olfactory tubercle and amygdala, whereas the pharmacological impact induced a slight but significant DA hyperinnervation in the nucleus accumbens. The cell densities of calbindin (CB) and parvalbumin (PV) positive neurons were additionally tested in the nucleus accumbens, but no significant effects were found. The present results contrast with the previously published long-term effects of early postnatal MA treatment that lead to a restraint of the maturation of DA fibres in the nucleus accumbens and prefrontal cortex and a concomitant overshoot innervation in the amygdala.ConclusionWe conclude that the morphogenetic properties of MA change during maturation and aging of gerbils, which may be due to physiological alterations of maturing vs. mature DA neurons innervating subcortical and cortical limbic areas. Our findings, together with results from other long-term studies, suggest that immature limbic structures are more vulnerable to persistent effects of a single MA intoxication; this might be relevant for the assessment of drug experience in adults vs. adolescents, and drug prevention programs.
Highlights
The aim of the study was to test long-term effects of (+)-methamphetamine (MA) on the dopamine (DA) innervation in limbo-cortical regions of adult gerbils, in order to understand better the repair and neuroplasticity in disturbed limbic networks
Quantitative DA data were obtained from a total of 327 sections that derived from 18 gerbils of two experimental groups (Saline n = 9, MA n = 9)
The overall DA fibre density in the nucleus accumbens (NAC) is selectively increased by MA [(ANOVA, F(1,16) = 4.7316, p = 0.0472) please note that analysis of variance (ANOVA) included comparison of 8 vs. 8 animals only, because some NAC sections were damaged in one animal of each experimental group]
Summary
The aim of the study was to test long-term effects of (+)-methamphetamine (MA) on the dopamine (DA) innervation in limbo-cortical regions of adult gerbils, in order to understand better the repair and neuroplasticity in disturbed limbic networks. This increasing number is especially alarming since it has been extensively shown that MA exerts acute neurotoxic effects on the monoaminergic transmitter systems, and leads to characteristic cognitive impairments like deficits in memory and learning, psychomotor speed and information processing [1]. It is especially affecting the dopamine (DA) neurons, leading to dramatic loss of fibres and other DAergic structures in certain brain areas within a few days [2,3], even after a single exposure [4]. This lab has further shown that the single early MA intoxication produces a loss of DA fibres and concomitant hyperinnervation of serotonin fibres in the nucleus accumbens (NAC) [15]
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