{"doi":"10.1101/2020.03.10.972687","title":"Effects of muscarinic M <sub>1</sub> receptor stimulation on reinforcing and neurochemical effects of cocaine in rats","abstract":"ABSTRACT Cocaine addiction is a chronic illness characterized by maladaptive drug-induced neuroplastic changes that confer lasting vulnerability to relapse. Over several weeks we observed the effects of the M 1 receptor-selective agonist VU0364572 in adult male rats that self-administer cocaine in a cocaine vs. natural reinforcer choice procedure. The drug showed unusual long-lasting effects, as rats gradually stopped self-administering cocaine, reallocating behavior towards the food reinforcer. The effect lasted as long as tested and at least four weeks. To begin to elucidate how VU0364572 modulates cocaine self-administration, we then examined its long-term effects using dual-probe in vivo dopamine and glutamate microdialysis in nucleus accumbens and medial prefrontal cortex, and ex vivo striatal dopamine reuptake. Microdialysis revealed dramatic decreases in cocaine-induced dopamine and glutamate outflow four weeks after VU0364572 treatment, without significant changes in dopamine uptake function. These lasting and dramatic effects of M 1 receptor stimulation reinforce our interest in this target as potential treatment of cocaine addiction. M 1 receptors are known to modulate medium spiny neuron responses to corticostriatal glutamatergic signaling acutely, and we hypothesize that VU0364572 may oppose the addiction-related effects of cocaine by causing lasting changes in this system.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2020,"id":129163,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":0,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9517,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2020-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":372188,"name":"Kathrine L. Jensen","orcid":"0000-0001-8985-9126","position":1,"is_corresponding":false},{"id":372189,"name":"Morgane Thomsen","orcid":"0000-0002-7250-6006","position":2,"is_corresponding":false},{"id":266023,"name":"Pia Weikop","orcid":"0000-0002-8422-1702","position":0,"is_corresponding":true}],"reference_count":74,"raw_metadata":null,"created_at":"2026-07-18T23:15:45.920615Z","pmid":null,"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":[]}