Caffeine – treat or trigger? Disparate behavioral and long-term dopaminergic changes in control and schizophrenia-like Wisket rats

• Main Authors: Adam, G. (Author), Benedek, G. (Author), Benyhe, S. (Author), Büki, A. (Author), Ducza, E. (Author), Horvath, G. (Author), Kekesi, G. (Author), Szűcs, E. (Author), Tuboly, G. (Author)
• Format: Article
• Language: English
• Published: Elsevier Inc. 2021
• Subjects: animal; animal experiment; animal model; Animals; Article; Behavior; body weight control; brain; Brain; brain cortex; brain region; caffeine; Caffeine; coffee consumption; cognition; Cognition; controlled study; dopamine; Dopamine; dopamine 2 receptor; Dopamine D2 receptor; dorsal striatum; exploratory behavior; fluorescence intensity; guanine nucleotide binding protein; hippocampus; human; Humans; in vitro study; ketamine; learning; locomotion; male; maximum binding capacity; messenger RNA; motor activity; nerve cell membrane; nociception; nonhuman; olfactory bulb; poly(methyl methacrylate); prefrontal cortex; Prefrontal Cortex; priority journal; rat; Rat; Rats; receptor binding assay; schizophrenia; Schizophrenia; sensory gating; startle reflex; videorecording
• Online Access: View Fulltext in Publisher

 The influence of caffeine on behavioral functions in both healthy and schizophrenic subjects is controversial. Here we aimed to reveal the effects of repeated caffeine pre- and post-training treatments on motor and exploratory activities and cognitive functions in a reward-based test (Ambitus) along with a brain region-specific dopamine D2 receptor profile in control and schizophrenia-like WISKET model rats. In the control animals, pre-treatment caused temporary enhancement in motor activity, while permanent improvement in learning function was detected in the WISKET animals. Post-treatment produced significant impairments in both groups. Caffeine caused short-lasting hyperactivity followed by a rebound in the inactive phase determined in undisturbed circumstance. Caffeine treatment substantially enhanced the dopamine D2 receptor mediated G-protein activation in the prefrontal cortex and olfactory bulb of both groups, while it increased in the dorsal striatum and cerebral cortex only in the WISKET animals. Caffeine enhanced the maximal binding capacity in the hippocampus and cerebral cortex of WISKET animals, but it decreased in the prefrontal cortex of the control animals. Regarding the dopamine D2 receptor mRNA expression, caffeine treatment caused significant enhancement in the prefrontal cortex of WISKET animals, while it increased the hippocampal dopamine D2 receptor protein amount in both groups. This study highlights the disparate effects of caffeine pre- versus post-training treatments on behavioral parameters in both control and schizophrenia-like animals and the prolonged changes in the dopaminergic system. It is supposed that the delayed depressive effects of caffeine might be compensated by frequent coffee intake, as observed in schizophrenic patients. © 2021 The Authors