Kisspeptin-8 Induces Anxiety-Like Behavior and Hypolocomotion by Activating the HPA Axis and Increasing GABA Release in the Nucleus Accumbens in Rats

Abstract

Kisspeptins (Kp) are RF-amide neuropeptide regulators of the reproductive axis that also influence anxiety, locomotion, and metabolism. We aimed to investigate the effects of intracerebroventricular Kp-8 (an N-terminally truncated octapeptide) treatment in Wistar rats. Elevated plus maze (EPM), computerized open field (OF), and marble burying (MB) tests were performed for the assessment of behavior. Serum LH and corticosterone levels were determined to assess kisspeptin1 receptor (Kiss1r) activation and hypothalamic-pituitary-adrenal axis (HPA) stimulation, respectively. GABA release from the nucleus accumbens (NAc) and dopamine release from the ventral tegmental area (VTA) and NAc were measured via ex vivo superfusion. Kp-8 decreased open arm time and entries in EPM, and also raised corticosterone concentration, pointing to an anxiogenic effect. Moreover, the decrease in arm entries in EPM, the delayed increase in immobility accompanied by reduced ambulatory activity in OF, and the reduction in interactions with marbles show that Kp-8 suppressed exploratory and spontaneous locomotion. The increase in GABA release from the NAc might be in the background of hypolocomotion by inhibiting the VTA-NAc dopaminergic circuitry. As Kp-8 raised LH concentration, it could activate Kiss1r and stimulate the reproductive axis. As Kiss1r is associated with hyperlocomotion, it is more likely that neuropeptide FF receptor activation is involved in the suppression of locomotor activity.

6-Methoxyflavone and Donepezil Behavioral Plus Neurochemical Correlates in Reversing Chronic Ethanol and Withdrawal Induced Cognitive Impairment

“…Concerning this, 6-MOF possesses an inherent GABA A agonist effect 23 and it has also been reported that an increased release of GABA in the nucleus accumbens results in hyperlocomotion that is mediated by inhibition of dopaminergic pathways in the ventral tegmental area and nucleus accumbens. 46 …”

Immunohistochemical Analysis of Neurotransmitters in Neurosecretory Protein GL-Producing Neurons of the Mouse Hypothalamus

“…Several synthetic bioactive peptides related to urocortin 3, growth hormone-releasing hormone, neuromedin U, and kisspeptin, have antidepressant-like or anxiety-like effects via the receptors for neurotransmitters or the release of neurotransmitters [ 45 , 46 , 47 , 48 ]. The dysregulations of neurotransmitters, including GABA and glutamate cause mood disorders and Alzheimer’s disease [ 49 , 50 ].…”

Immune Influencers in Action: Metabolites and Enzymes of the Tryptophan-Kynurenine Metabolic Pathway

“…Depression, anxiety and cognitive impairment are the most common symptoms of psychiatric disorders that may concur and/or sway during progression and comorbidity frequently occurs in mental illnesses, which renders the exact diagnosis even more difficult. Scrupulous studies are underway to untangle the thread of pathophysiology of mental disorders and their comorbidities not only in clinical medicine, but also in animal studies [106][107][108][109]. Psychological stress, especially depression has been found to be a risk factor for dementia, a prognostic biomarker for stokes and a therapeutic target for meaning-centered psychotherapy in depression, and animal-assisted and pet-robot interventions in dementia [110][111][112][113].…”