Effects of intrastriatal dopamine D1 or D2 antagonists on methamphetamine-induced egocentric and allocentric learning and memory deficits in Sprague–Dawley rats

Abstract

Rationale: Methamphetamine (MA) is an abused psychostimulant that causes cognitive deficits after chronic use. Neostriatal dopamine receptors play a role in MA monoamine neurotoxicity. Blocking dopamine receptors prior to MA exposure in adult rats attenuates monoamine reductions and reactive gliosis. Objectives: We tested whether blocking dopamine receptors protects against cognitive deficits. Methods: First, we determined the effects of MA alone versus MA in combination with the dopamine receptor D1 antagonist SCH-23390 or the dopamine receptor D2 antagonist sulpiride on cFos expression and monoamines at the age when rats in the cognitive experiment were to begin testing and monoamines in rats after cognitive testing. Results: SCH-23390 infused into the neostriatum prior to systemic administration of MA attenuated MA-induced cFos activation while sulpiride induced cFos activation. Two weeks after MA, rats had dopamine and serotonin reductions that were attenuated by each antagonist. Other rats treated the same way, were tested for egocentric learning and memory in the Cincinnati water maze, for navigational strategy in a star water maze, and spatial learning and memory in a Morris water maze. Pretreatment with SCH-23390 or sulpiride attenuated the effects of MA on egocentric and spatial learning and memory. MA-treated rats showed a shift from an egocentric to a disorganized strategy in the Star maze that was less disorganized in groups receiving MA and an antagonist. Post-behavior monoamine reductions remained but were attenuated by the antagonists but not identically to what was seen in rats not behaviorally tested. Conclusions: The results show for the first time that dopamine receptors are mediators of MAinduced cognitive deficits.

Transformer maze for the evaluation of the learning and memory in rodents

“…Spatial navigation requires egocentric and allocentric strategies, meaning that the animal is guided simultaneously by the cues and features of the routes. These mechanisms are mediated by various neurochemical pathways ( Rubio et al., 2012 ; Gutierrez et al., 2019 ). Disturbances of DA metabolism in DAT-HET rats may lead to impaired functioning and integration of these different systems.…”

“…Disturbances of DA metabolism in DAT-HET rats may lead to impaired functioning and integration of these different systems. Previously it has been shown, that methamphetamine impairs both egocentric and allocentric learning and memory ( Gutierrez et al., 2019 ).…”

Krill Oil Alleviated Methamphetamine-Induced Memory Impairment via the MAPK Signaling Pathway and Dopaminergic Synapse Pathway

“…There are five types of dopamine receptors grouped into two major subclasses: DRD1-like, including DRD1 and D1RD5, and DRD2-like, including DRD2, DRD3, and DRD4, which often interact to regulate neurotransmission . Repeated METH exposure could increase the protein expression of DRD2 in the hippocampus area and reduce the protein expression of DAT (Zhou et al, 2019), and pretreatment with DRD2 antagonist sulpiride attenuated the effects of METH on egocentric and spatial learning and memory (Gutierrez et al, 2019). DAT-KO rats demonstrated deficits in sensorimotor gating and working memory tests (Leo et al, 2018).…”

The Role of Zebrafish and Laboratory Rodents in Schizophrenia Research

“…In example, sulpiride (as a selective antagonist of D 2 and D 3 receptors) did not reverse MK-801 disrupted PPI in rats (278) and risperidone (as SDA) did not normalize PCP induced impairments in learning and executive functions by subchronic administration of PCP in rats (244), when in contrary the cognitive deficits are often ameliorated by clozapine and olanzapine (MARTA antipsychotics) (200,259,(267)(268)(269)(270)(271)(272)(283)(284)(285). On the other hand, risperidone normalized some cognitive symptoms induced by MK-801 and by hippocampal lesions (249,273), whereas sulpiride normalized cognitive symptoms induced by metamphetamine (274). Partial dopamine receptor agonist aripiprazole interacting as agonist with D 2 and 5-HT 1A and as antagonist with 5-HT 2A receptors has been shown to normalize cognitive symptoms (275,276) and act neuroprotectivelly via reduction of apoptosis in PFC, even when administered repeatedly.…”