{"doi":"10.3389/fphar.2022.895006","title":"Memantine Attenuates Cocaine and neuroHIV Neurotoxicity in the Medial Prefrontal Cortex","abstract":"Individuals with substance use disorder are at a higher risk of contracting HIV and progress more rapidly to AIDS as drugs of abuse, such as cocaine, potentiate the neurotoxic effects of HIV-associated proteins including, but not limited to, HIV-1 trans-activator of transcription (Tat) and the envelope protein Gp120. Neurotoxicity and neurodegeneration are hallmarks of HIV-1-associated neurocognitive disorders (HANDs), which are hypothesized to occur secondary to excitotoxicity from NMDA-induced neuronal calcium dysregulation, which could be targeted with NMDA antagonist drugs. Multiple studies have examined how Gp120 affects calcium influx and how cocaine potentiates this influx; however, they mostly focused on single cells and did not analyze effects in neuronal and vascular brain networks. Here, we utilize a custom multi-wavelength imaging platform to simultaneously study the neuronal activity (detected using genetically encoded Ca 2+ indicator, GcaMP6f, expressed in neurons) and hemodynamic changes (measured by total hemoglobin and oxygenated hemoglobin within the tissue) in the prefrontal cortex (PFC) of HIV-1 Tg rats in response to cocaine and evaluate the effects of the selective NMDA antagonist drug memantine on cocaine and HIV neurotoxicity compared to those of non-HIV-1 Tg animals (controls). Our results show that memantine improved cocaine-induced deficit in cerebral blood volume while also attenuating an abnormal increase of the neuronal calcium influx and influx duration in both control rats and HIV-1 Tg rats. Cocaine-induced neuronal and hemodynamic dysregulations were significantly greater in HIV-1 Tg rats than in control rats. With memantine pretreatment, HIV-1 Tg rats showed attenuated cocaine’s effects on neuronal and hemodynamic responses, with responses similar to those observed in control rats. These imaging results document an enhancement of neuronal Ca 2+ influx, hypoxemia, and ischemia with cocaine in the PFC of HIV-1 Tg rats that were attenuated by memantine pretreatment. Thus, the potential utility of memantine in the treatment of HAND and of cocaine-induced neurotoxicity deserves further investigation.","journal":"Frontiers in Pharmacology","year":2022,"id":272758,"datarank":0.37273599746820013,"base_score":2.4849066497880004,"endowment":2.4849066497880004,"self_citation_contribution":0.37273599746820013,"citation_network_contribution":0.0,"self_endowment_contribution":0.37273599746820013,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":11,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9566,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2022-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":932511,"name":"Yueming Hua","orcid":null,"position":1,"is_corresponding":false},{"id":347870,"name":"Kevin Clare","orcid":"0000-0003-0300-6080","position":2,"is_corresponding":false},{"id":393590,"name":"Kicheon Park","orcid":"0000-0003-4863-4398","position":3,"is_corresponding":false},{"id":716974,"name":"Craig P. Allen","orcid":"0000-0001-8370-3884","position":4,"is_corresponding":false},{"id":109148,"name":"Nora D. Volkow","orcid":"0000-0001-6668-0908","position":5,"is_corresponding":false},{"id":530380,"name":"Xiu‐Ti Hu","orcid":"0000-0002-4463-2216","position":6,"is_corresponding":false},{"id":393591,"name":"Yingtian Pan","orcid":"0000-0002-7635-1443","position":7,"is_corresponding":false},{"id":393592,"name":"Congwu Du","orcid":"0000-0001-8957-4366","position":0,"is_corresponding":true}],"reference_count":62,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-19T00:27:47.926496Z","pmid":"35694269","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}