Behavioral anxiolysis without reduction of hippocampal theta frequency after histamine application in the lateral septum of rats

Abstract

Hippocampal theta activity is linked to various processes, including locomotion, learning and memory, and defense and affect (i.e., fear and anxiety). Interestingly, all classes of clinically effective anxiolytics, as well as experimental compounds that decrease anxiety in pre-clinical animal models of anxiety, reduce the frequency of hippocampal theta activity elicited by stimulation of the reticular formation in freely behaving or anesthetized animals. In the present experiments, we found that bilateral histamine infusions (0.5 µg/hemisphere) into the lateral septum (LS) of rats decreased anxiety-like responses in two models of anxiety, the elevated plus maze and novelty-induced suppression of feeding test. Surprisingly, these same infusions significantly increased hippocampal theta frequency elicited by reticular stimulation in urethane-anesthetized rats. In contrast to these findings, additional experiments showed that the clinically effective anxiolytic buspirone (40 mg/kg, i.p.) reduced theta frequency, confirming previous observations. Taken together, the dissociation of behavioral anxiolysis and theta frequency reduction noted here suggest that hippocampal theta frequency is not a direct index of anxiety levels in rodents. Further, the mechanisms underlying the behavioral and physiological effects elicited by histamine in the LS require further study.

Anxious and Nonanxious Mice Show Similar Hippocampal Sensory Evoked Oscillations under Urethane Anesthesia: Difference in the Effect of Buspirone

“…Male mice of 2.5–3 months were housed individually under a light/dark 12 h cycle (lights on at 08:00) at 24 ± 1°C and given ad libitum food and water. Mice were handled for 7 days prior to testing, the procedure is described by Hurst and West [ 13 ]. For the experiments, 55–59th generations were used.…”

“…Of particular interest here, almost all classes of clinically effective anxiolytics and compounds in the preclinical stage reduce the frequency of hippocampal theta activity elicited by stimulation of the reticular formation in freely behaving or anesthetized animals [ 12 ]. Notable exception includes direct bilateral histamine infusion into the lateral septum, which decreased anxiety-like responses in two models of anxiety, the elevated plus maze and novelty-induced suppression of feeding test in rats, but, instead of decreasing, the same infusion significantly increased hippocampal theta frequency elicited by reticular stimulation in urethane-anesthetized rats [ 13 ]. Similar results were reported for direct septal infusion of muscimol, which also increased theta frequency evoked by brainstem stimulation and reduced anxiety-like behaviors [ 14 ].…”

Ascending Control of Arousal and Motivation: Role of Nucleus Incertus and its Peptide Neuromodulators in Behavioural Responses to Stress

“…In addition to the mnemonic roles of the hippocampus and theta rhythm, this circuit also functions to modulate interrelated emotional and social behaviour. For example, the lateral septum is an essential negative regulator of lordosis/sociosexual and anxiety‐like behaviour , which is also strongly modulated by the ventral hippocampus . Recent studies also indicate that a specific subclass of interneurones in the prefrontal cortex, which is a primary NI input area and receives moderate NI projections, mediate changes in female sociosexual behaviour in response to oxytocin .…”

Targeting the Modulation of Neural Circuitry for the Treatment of Anxiety Disorders

“…A reduction of hippocampal theta activity has also been implicated in the anxiolysis induced by various classes of anxiolytics, including buspirone (McNaughton et al, 2007;Chee et al, 2014). A reduction of hippocampal theta activity has also been implicated in the anxiolysis induced by various classes of anxiolytics, including buspirone (McNaughton et al, 2007;Chee et al, 2014).…”

“…A reduction of hippocampal theta activity has also been implicated in the anxiolysis induced by various classes of anxiolytics, including buspirone (McNaughton et al, 2007;Chee et al, 2014). A reduction of hippocampal theta activity has also been implicated in the anxiolysis induced by various classes of anxiolytics, including buspirone (McNaughton et al, 2007;Chee et al, 2014). McNaughton et al (2013) proposed that conflict-specific, right frontal activation recorded noninvasively with surface electrodes is a readily obtainable noninvasive human functional homolog of rodent hippocampal-cortical activity that may also be useful as an objective biologic marker of anxiolytic efficacy.…”