Prelimbic α1-adrenoceptors are involved in the regulation of depressive-like behaviors in the hemiparkinsonian rats

Brain Res Bull. 2017 Sep:134:99-108. doi: 10.1016/j.brainresbull.2017.07.011. Epub 2017 Jul 14.

Abstract

At present, it is not clear whether α1-adrenoceptors in the prelimbic cortex (PrL) are involved in Parkinson's disease-related depression. Here we examined effects of PrL α1-adrenoceptors on depressive-like behaviors in rats with unilateral 6-hydroxydopamine lesions of the medial forebrain bundle. The lesion induced depressive-like responses as measured by the sucrose preference and forced swim tests compared to sham-operated rats. Intra-PrL injection of α1-adrenoceptor agonist phenylephrine induced or increased the expression of depressive-like behaviors in sham-operated and the lesioned rats. Further, intra-PrL injection of α1-adrenoceptor antagonist benoxathian produced antidepressant effects in two groups of rats. Intra-PrL injection of phenylephrine increased the mean firing rate of PrL pyramidal neurons in both sham-operated and the lesioned rats, while benoxathian decreased the mean firing rate of the neurons. Compared to sham-operated rats, the duration of phenylephrine and benoxathian action on the firing rate of the pyramidal neurons was shortened in the lesioned rats. Neurochemical results showed that intra-PrL injection of phenylephrine or benoxathian increased or decreased dopamine and noradrenaline and serotonin levels in the medial prefrontal cortex, ventral hippocampus and habenula in sham-operated and the lesioned rats, respectively. Altogether, these results suggest that activation and blockade of α1-adrenoceptors in the PrL change the firing activity of the pyramidal neurons, and then increase or decrease levels of three monoamines in the limbic and limbic-related brain regions, which are involved in the regulation of depressive-like behaviors. Additionally, the results also suggest that the dopaminergic lesion leads to hypofunctionality of α1-adrenoceptors on pyramidal neurons of the PrL.

Keywords: Depression; Parkinson’s disease; Prelimbic cortex; Rat; α(1)-Adrenoceptors.

MeSH terms

  • Action Potentials / drug effects
  • Action Potentials / physiology
  • Adrenergic alpha-1 Receptor Agonists / pharmacology
  • Adrenergic alpha-1 Receptor Antagonists / pharmacology
  • Animals
  • Antidepressive Agents / pharmacology
  • Antiparkinson Agents / pharmacology
  • Brain / drug effects
  • Brain / metabolism*
  • Depression / etiology
  • Depression / metabolism*
  • Dopamine / metabolism
  • Functional Laterality
  • Male
  • Norepinephrine / metabolism
  • Oxathiins / pharmacology
  • Parkinsonian Disorders / complications
  • Parkinsonian Disorders / metabolism*
  • Parkinsonian Disorders / psychology*
  • Phenylephrine / pharmacology
  • Pyramidal Cells / drug effects
  • Pyramidal Cells / metabolism
  • Rats, Sprague-Dawley
  • Receptors, Adrenergic, alpha-1 / metabolism*
  • Serotonin / metabolism

Substances

  • Adrenergic alpha-1 Receptor Agonists
  • Adrenergic alpha-1 Receptor Antagonists
  • Antidepressive Agents
  • Antiparkinson Agents
  • Oxathiins
  • Receptors, Adrenergic, alpha-1
  • Phenylephrine
  • Serotonin
  • benoxathian
  • Dopamine
  • Norepinephrine