scholarly journals Effects of Mephedrone and Amphetamine Exposure during Adolescence on Spatial Memory in Adulthood: Behavioral and Neurochemical Analysis

2021 ◽  
Vol 22 (2) ◽  
pp. 589
Author(s):  
Pawel Grochecki ◽  
Irena Smaga ◽  
Malgorzata Lopatynska-Mazurek ◽  
Ewa Gibula-Tarlowska ◽  
Ewa Kedzierska ◽  
...  
Keyword(s):  
Prefrontal Cortex ◽  
Nmda Receptor ◽  
Spatial Memory ◽  
Reversal Learning ◽  
Drug Effects ◽  
Long Term Effects ◽  
Delayed Effect ◽  
Adult Rats ◽  
Neurochemical Analysis ◽  
Learning Impairment

A synthetic cathinone, mephedrone is widely abused by adolescents and young adults. Despite its widespread use, little is known regarding its long-term effects on cognitive function. Therefore, we assessed, for the first time, whether (A) repeated mephedrone (30 mg/kg, i.p., 10 days, once a day) exposure during adolescence (PND 40) induces deleterious effects on spatial memory and reversal learning (Barnes maze task) in adult (PND 71–84) rats and whether (B) these effects were comparable to amphetamine (2.5 mg/kg, i.p.). Furthermore, the influence of these drugs on MMP-9, NMDA receptor subunits (GluN1, GluN2A/2B) and PSD-95 protein expression were assessed in adult rats. The drug effects were evaluated at doses that per se induce rewarding/reinforcing effects in rats. Our results showed deficits in spatial memory (delayed effect of amphetamine) and reversal learning in adult rats that received mephedrone/amphetamine in adolescence. However, the reversal learning impairment may actually have been due to spatial learning rather than cognitive flexibility impairments. Furthermore, mephedrone, but not amphetamine, enhanced with delayed onset, MMP-9 levels in the prefrontal cortex and the hippocampus. Mephedrone given during adolescence induced changes in MMP-9 level and up-regulation of the GluN2B-containing NMDA receptor (prefrontal cortex and hippocampus) in young adult (PND 63) and adult (PND 87) rats. Finally, in adult rats, PSD-95 expression was increased in the prefrontal cortex and decreased in the hippocampus. In contrast, in adult rats exposed to amphetamine in adolescence, GluN2A subunit and PSD-95 expression were decreased (down-regulated) in the hippocampus. Thus, in mephedrone—but not amphetamine-treated rats, the deleterious effects on spatial memory were associated with changes in MMP-9 level. Because the GluN2B-containing NMDA receptor dominates in adolescence, mephedrone seems to induce more harmful effects on cognition than amphetamine does during this period of life.

scholarly journals Rapamycin Improves Spatial Learning Deficits, Vulnerability to Alcohol Addiction and Altered Expression of the GluN2B Subunit of the NMDA Receptor in Adult Rats Exposed to Ethanol during the Neonatal Period

Biomolecules ◽  
2021 ◽  
Vol 11 (5) ◽  
pp. 650
Author(s):  
Malgorzata Lopatynska-Mazurek ◽  
Anna Antolak ◽  
Pawel Grochecki ◽  
Ewa Gibula-Tarlowska ◽  
Anna Bodzon-Kulakowska ◽  
...  
Keyword(s):  
Nmda Receptor ◽  
Spatial Memory ◽  
Spatial Learning ◽  
Reversal Learning ◽  
Neonatal Period ◽  
Ethanol Exposure ◽  
Control Group ◽  
Adult Rats ◽  
Altered Expression ◽  
The Impact

Ethanol exposure during pregnancy alters the mammalian target of rapamycin (mTOR) signaling pathway in the fetal brain. Hence, in adult rats exposed to ethanol during the neonatal period, we investigated the influence of rapamycin, an mTOR Complex 1 (mTORC1) inhibitor, on deficits in spatial memory and reversal learning in the Barnes maze task, as well as the ethanol-induced rewarding effects (1.0 or 1.5 g/kg) using the conditioning place preference (CPP) paradigm. Rapamycin (3 and 10 mg/kg) was given before intragastric ethanol (5 g/kg/day) administration at postnatal day (PND)4–9 (an equivalent to the third trimester of human pregnancy). Spatial memory/reversal learning and rewarding ethanol effect were evaluated in adult (PND60–70) rats. Additionally, the impact of rapamycin pre-treatment on the expression of the GluN2B subunit of NMDA receptor in the brain was assessed in adult rats. Our results show that neonatal ethanol exposure induced deficits in spatial memory and reversal learning in adulthood, but the reversal learning outcome may have been due to spatial learning impairments rather than cognitive flexibility impairments. Furthermore, in adulthood the ethanol treated rats were also more sensitive to the rewarding effect of ethanol than the control group. Rapamycin prevented the neonatal effect of ethanol and normalized the GluN2B down-regulation in the hippocampus and the prefrontal cortex, as well as normalized this subunit’s up-regulation in the striatum of adult rats. Our results suggest that rapamycin and related drugs may hold promise as a preventive therapy for fetal alcohol spectrum disorders.

scholarly journals Phencyclidine administration during neurodevelopment alters network activity in prefrontal cortex and hippocampus in adult rats

2017 ◽  
Vol 118 (2) ◽  
pp. 1002-1011 ◽  
Author(s):  
Celia Kjaerby ◽  
Nanna Hovelsø ◽  
Nils Ole Dalby ◽  
Florence Sotty
Keyword(s):  
Prefrontal Cortex ◽  
Nmda Receptor ◽  
Receptor Antagonist ◽  
Gamma Oscillations ◽  
Nmda Receptor Antagonist ◽  
Theta Oscillations ◽  
Network Activity ◽  
Adult Rats ◽  
Functional Deficits ◽  
Acute Challenge

We show that insults with a NMDA receptor antagonist during neurodevelopment lead to suppressed evoked theta oscillations in ventral hippocampus in adult rats, while evoked gamma oscillations are enhanced and hypersensitive to an acute challenge with a NMDA receptor antagonist in prefrontal cortex. These observations reveal the significance of neurodevelopmental disturbances in the evolvement of schizophrenia-like symptoms and contribute to the understanding of the functional deficits underlying aberrant behavior in this disease.

An Increase in Aβ42 in the Prefrontal Cortex is Associated with a Reversal-Learning Impairment in Alzheimers Disease Model Tg2576 APPsw Mice

2008 ◽  
Vol 5 (4) ◽  
pp. 385-391 ◽  
Author(s):  
Jia-Min Zhuo ◽  
Annamalai Prakasam ◽  
Melissa Murray ◽  
Hai-Yan Zhang ◽  
Mark Baxter ◽  
...  
Keyword(s):  
Prefrontal Cortex ◽  
Reversal Learning ◽  
Disease Model ◽  
Alzheimers Disease ◽  
Learning Impairment

scholarly journals Alcohol Consumption during Adulthood Does Not Impair Later Go/No-Go Reversal Learning in Male Rats

NeuroSci ◽  
2021 ◽  
Vol 2 (2) ◽  
pp. 166-176
Author(s):  
Charles L. Pickens ◽  
Mark Gallo ◽  
Hayley Fisher ◽  
Alisa Pajser ◽  
Madelyn H. Ray
Keyword(s):  
Alcohol Consumption ◽  
Reversal Learning ◽  
Drugs Of Abuse ◽  
Alcohol Exposure ◽  
Male Rats ◽  
Laboratory Animals ◽  
Long Term Effects ◽  
Adult Rats ◽  
Higher Alcohol

Reversal learning tasks are used to model flexible decision-making in laboratory animals, and exposure to drugs of abuse can cause long-term impairments in reversal learning. However, the long-term effects of alcohol on reversal learning have varied. We evaluated whether six weeks of voluntary alcohol consumption through chronic intermittent alcohol access (elevated by food restriction) in adult male rats would impair rats in a go/no-go reversal learning task when tested at an interval beyond acute withdrawal. In our go/no-go task, rats were reinforced for pressing one lever or withholding from pressing another lever, and the identities of the two levers were switched twice (once rats reached an accuracy criterion). We found no evidence that prior alcohol consumption altered discrimination or reversal learning in our task. This replicates previous patterns from our laboratory that higher alcohol consumption in food-restricted rats did not impair discrimination or reversal learning in a different go/no-go task and that alcohol consumption in free-fed adolescent/early adult rats did not impair go/no-go discrimination or reversal learning in the same task. It is unclear whether this represents an insensitivity of this task to alcohol exposure generally or whether an alcohol exposure procedure that leads to higher blood ethanol concentration (BEC) levels would impair learning. More research is needed to investigate these possibilities.

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