Caffeine enhances BOLD responses to electrical whisker pad stimulation in rats during alpha‐chloralose anaesthesia

• Published in: The European journal of neuroscience 2021-01, Vol.53 (2), p.601-610
• Main Authors: Shih, Cheng‐Ting, Chiu, Shao‐Chieh, Peng, Shin‐Lei
• Format: Article
• Language: English
• Subjects: anaesthesia; Anesthesia; Animal models; Blood flow; Blood pressure; Caffeine; Cerebral blood flow; cerebral metabolism; Cortex (somatosensory); deoxyhaemoglobin; Functional magnetic resonance imaging; Injection; Vibrissae
• ISSN: 0953-816X; 1460-9568
• DOI: 10.1111/ejn.14968

By reducing the cerebral blood flow and thereby increasing the resting deoxyhaemoglobin concentration, many human studies have shown that caffeine has a beneficial effect on enhancing the magnitude of blood‐oxygenation‐level‐dependent (BOLD) responses. However, the effect of caffeine on BOLD responses in animals under anaesthesia has not been demonstrated. In this study, we aimed to determine the effect of systemic caffeine administration on BOLD responses in rats under alpha‐chloralose. By applying electric whisker pad stimulation to male Sprague‐Dawley rats, we performed fMRI measurements before and after the caffeine injection (40 mg/kg, n = 7) or an equivalent volume of saline (n = 6) at 7T. To understand the potential perturbation of animal physiology during stimulation, arterial blood pressure was measured in a separate group of animals (n = 3) outside the scanner. Caffeine significantly decreased baseline BOLD signals (p = .05) due to the increased deoxyhaemoglobin level. Both BOLD responses and t‐values in the primary somatosensory cortex were significantly increased (both p  .05). No significant differences in BOLD responses and t‐values were observed in the control condition of saline injection (both p > .05). These findings suggested that, although the cerebral activity was lower under alpha‐chloralose anaesthesia, the higher level of deoxygemoglobin at the baseline under the caffeinated condition can benefit the magnitude of BOLD responses in rats. These findings suggest that animal models might serve as potential platforms for further caffeine‐related fMRI research studies. The blood‐oxygenation‐level‐dependent (BOLD) responses related to whisker pad stimulation were significantly enhanced in rats under alpha‐chloralose anaesthesia with pharmacological modulation of caffeine. We speculate that because of the increased deoxyhaemoglobin level in this baseline state, caffeine exerts an effect on augmenting positive BOLD responses.