Behavioural, neurochemical and neuroendocrine effects of the endogenous β-carboline harmane in fear-conditioned rats
| Autor: | David S. Jessop, Karen L. Smith, Gemma K. Ford, David P. Finn |
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| Rok vydání: | 2012 |
| Předmět: |
Male
Serotonin medicine.medical_specialty Dopamine Conditioning Classical Pituitary-Adrenal System Pharmacology Hippocampus Rats Sprague-Dawley Norepinephrine chemistry.chemical_compound Neurochemical Adrenocorticotropic Hormone Corticosterone Internal medicine Conditioning Psychological Monoaminergic medicine Animals Pharmacology (medical) Fear conditioning Harmane Behavior Animal Fear Rats Harmine Psychiatry and Mental health Monoamine neurotransmitter Endocrinology chemistry Psychology Carbolines medicine.drug |
| Zdroj: | Journal of Psychopharmacology. 27:162-170 |
| ISSN: | 1461-7285 0269-8811 |
| Popis: | The putative endogenous imidazoline binding site ligand harmane enhances neuronal activation in response to psychological stress and alters behaviour in animal models of anxiety and antidepressant efficacy. However, the neurobiological mechanisms underlying harmane’s psychotropic effects are poorly understood. We investigated the effects of intraperitoneal injection of harmane (2.5 and 10 mg/kg) on fear-conditioned behaviour, hypothalamo-pituitary-adrenal axis activity, and monoaminergic activity within specific fear-associated areas of the rat brain. Harmane had no significant effect on the duration of contextually induced freezing or 22 kHz ultrasonic vocalisations and did not alter the contextually induced suppression of motor activity, including rearing. Harmane reduced the duration of rearing and tended to increase freezing in non-fear-conditioned controls, suggesting potential sedative effects. Harmane increased plasma ACTH and corticosterone concentrations, and serotonin (in hypothalamus, amygdaloid cortex, prefrontal cortex and hippocampus) and noradrenaline (prefrontal cortex) content, irrespective of fear-conditioning. Furthermore, harmane reduced dopamine and serotonin turnover in the PFC and hypothalamus, and serotonin turnover in the amygdaloid cortex in both fear-conditioned and non-fear-conditioned rats. In contrast, harmane increased dopamine and noradrenaline content and reduced dopamine turnover in the amygdala of fear-conditioned rats only, suggesting differential effects on catecholaminergic transmission in the presence and absence of fear. The precise mechanism(s) mediating these effects of harmane remain to be determined but may involve its inhibitory action on monoamine oxidases. These findings support a role for harmane as a neuromodulator, altering behaviour, brain neurochemistry and neuroendocrine function. |
| Databáze: | OpenAIRE |
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