Gestational treatment with methylazoxymethanol (MAM) that disrupts hippocampal-dependent memory does not alter behavioural response to cocaine

• Published in: Pharmacology, biochemistry and behavior biochemistry and behavior, 2009-10, Vol.93 (4), p.382-390
• Main Authors: Featherstone, Robert E., Burton, Christie L., Coppa-Hopman, Romina, Rizos, Zoë, Sinyard, Judy, Kapur, Shitij, Fletcher, Paul J.
• Format: Article
• Language: English
• Subjects: Adult and adolescent clinical studies; Alkylating Agents - pharmacology; Animal model; Animals; Behavior, Animal - drug effects; Biological and medical sciences; Brain - anatomy & histology; Brain - drug effects; Cocaine - pharmacology; Cocaine-Related Disorders - psychology; Conditioning, Operant - drug effects; Dopamine; Dose-Response Relationship, Drug; Drug-induced reinstatement; Extinction, Psychological - drug effects; Female; Hippocampus; Hippocampus - physiology; Learning - drug effects; Maze Learning - drug effects; Medical sciences; Memory; Memory - drug effects; Methylazoxymethanol Acetate - analogs & derivatives; Methylazoxymethanol Acetate - pharmacology; Motor Activity - drug effects; Neuropharmacology; Organ Size - drug effects; Pharmacology. Drug treatments; Pregnancy; Progressive ratio schedule of reinforcement; Psychoanaleptics: cns stimulant, antidepressant agent, nootropic agent, mood stabilizer; Psychoanaleptics: cns stimulant, antidepressant agent, nootropic agent, mood stabilizer..., (alzheimer disease); Psychology. Psychoanalysis. Psychiatry; Psychopathology. Psychiatry; Psychopharmacology; Psychoses; Rats; Rats, Sprague-Dawley; Reinforcement Schedule; Schizophrenia; Self-administration
• ISSN: 0091-3057; 1873-5177
• DOI: 10.1016/j.pbb.2009.05.010

Schizophrenia is associated with increased rates of substance abuse that are thought to be the result of changes in cortical and mesolimbic dopamine activity. Previous work has shown that gestational methylazoxymethanol acetate (MAM) treatment induces increased mesolimbic dopamine activity when given around the time of embryonic day 17 (ED17), suggesting that MAM treatment may model some aspects of schizophrenia. Given that increased dopaminergic activity facilitates aspects of drug self-administration and reinstatement of drug seeking, the current experiments sought to assess cocaine self-administration in MAM treated animals. Experiment 1 examined the acquisition of cocaine self-administration in ED17 MAM and saline treated rats using a sub-threshold dose of cocaine. In experiment 2 ED17 MAM and saline treated animals were trained to self-administer cocaine and were then assessed under varying doses of cocaine (dose–response), followed by extinction and drug-induced reinstatement of responding. A subset of these animals was trained on a win-shift radial maze task, designed to detect impairments in hippocampal-dependent memory. In experiment 3, MAM and saline treated animals were assessed on a progressive ratio schedule of cocaine delivery. Finally, in experiment 4 MAM and saline treated animals were assessed on cocaine-induced locomotor activity across a range of doses of cocaine. MAM treatment disrupted performance of the win-shift task but did not alter cocaine self-administration or cocaine-induced locomotion. Implications of these results for the MAM model of schizophrenia are discussed.