RESUMEN
The increasing prevalence of obesity and eating disorders makes identifying neural substrates controlling eating and regulating body weight a priority. Recent studies have highlighted the role of the lateral septum (LS) in eating control mechanisms. The current study explored the roles of gamma-aminobutyric acid (GABA) receptors within the LS in the control of food intake. Experiments with a rat model (n ≥ 11/group) showed that LS microinjection of the GABAA receptor agonist, muscimol, and the GABAB receptor agonist, baclofen hydrochloride (baclofen), elicited intense, dose-dependent feeding. In contrast, LS pretreatment with the GABAA receptor antagonist, picrotoxin, markedly reduced the muscimol-elicited feeding, and pretreatment injections with the GABAB receptor antagonist, 2-hydroxysaclofen (2-OH saclofen), reduced the baclofen evoked response. Next, we showed that picrotoxin injection at the beginning of the dark phase of the light-dark cycle-when rats show a burst of spontaneous eating-reduced naturally occurring feeding, whereas 2-OH saclofen was ineffective. These results indicate that the activation of LS GABAA and GABAB receptors strongly stimulates feeding and suggests potential roles in feeding control neurocircuitry. In particular, our evidence indicates that endogenous LS GABA and GABAA receptors may be involved in mediating naturally occurring nocturnal feeding.
RESUMEN
The lateral septum (LS), a brain region typically associated with behaviors involving reward, anxiety-like behavior, learning, and memory, has recently received increased interest due to its potential role in eating behavior. Our current results showed that morphine (5 µg) microinjected into the LS produced a stable feeding response. Specifically, across five days of repeated injections, there was no increase or sensitization effect, nor a decrease in feeding or tolerance. Additionally, we found that pretreatment with the broad-spectrum opioid receptor antagonist naloxone blocked morphine-elicited feeding, further supporting a role for LS opioid receptors in the activation of feeding behaviors. We had previously found that the GABAA receptor agonist muscimol produces a similar increase in feeding when injected into the LS. Given the involvement of the LS in multiple behaviors, we next evaluated whether other behaviors might be co-occurring with feeding in response to opioid or GABAA receptor agonist injection into the LS. We assessed eating, drinking, grooming, sleeping, activity levels and resting behavior for 3 h after injection of aCSF, DAMGO, morphine, or muscimol. We found that morphine and muscimol both decreased the latency to eat, and all drugs tested increased food intake. The feeding occurred within 30 min of muscimol injection but was delayed after opioid injections. The absence of increases in other goal-oriented behavior like drinking or grooming or behavioral hyperactivity supports a primary effect of muscimol and the opioids on LS mechanisms of feeding control. SIGNIFICANCE STATEMENT: The LS is interesting because of its role in a wide range of behaviors including defensive behaviors, social behaviors, learning, memory, and motivation. Although the LS was discovered to have a role in feeding stimulation over 30 years ago, only recently has major progress begun to reveal the underlying mechanisms. The present paper contributes by suggesting that LS GABAA and µ-opioid receptors elicit eating by inhibiting LS neurons that themselves inhibit eating. Importantly, this work informs lateral septal research which may shed light on disordered eating included binge eating and anorexia.