Hypophysectomy-induced striatal hypersensitivity and mesolimbic hyposensitivity to apomorphine

Area of Science:

• Neuroscience
• Endocrinology
• Pharmacology

Background:

• Hypophysectomy, the surgical removal of the pituitary gland, significantly impacts hormonal regulation.
• Dopamine systems in the brain, particularly in the nucleus accumbens septi and striatum, are crucial for regulating motor activity and stereotyped behaviors.
• Apomorphine is a non-selective dopamine receptor agonist used to probe dopamine system function.

Purpose of the Study:

• To investigate the neurochemical and behavioral adaptations in female rats following hypophysectomy.
• To characterize the changes in dopamine receptor sensitivity and neurotransmitter activity in specific brain regions after hypophysectomy.
• To evaluate the hypophysectomized female rat as a model for studying distinct dopamine pathways.

Main Methods:

• Female rats underwent hypophysectomy and were tested at 7 and 28 days post-surgery.
• Locomotor activity and stereotypy were assessed following apomorphine administration.
• Neurochemical analyses included measuring 3H-spiroperidol binding (dopamine D2 receptor density) and tyrosine hydroxylase activity (dopamine synthesis marker) in the nucleus accumbens septi and striatum.

Main Results:

• At 7 days post-hypophysectomy, rats showed hyposensitivity to locomotor effects and hypersensitivity to stereotypy effects of apomorphine.
• Neurochemically, this correlated with decreased 3H-spiroperidol binding and increased tyrosine hydroxylase activity in the nucleus accumbens septi.
• At 28 days post-hypophysectomy, rats were hypersensitive to both locomotor and stereotypy effects, associated with increased 3H-spiroperidol binding and decreased tyrosine hydroxylase activity in the nucleus accumbens septi.
• Increased apomorphine-induced stereotypy in both groups was linked to increased 3H-spiroperidol binding and decreased tyrosine hydroxylase activity in the striatum.

Conclusions:

• Hypophysectomy induces a transient decrease in dopamine receptor sensitivity in the nucleus accumbens septi of female rats.
• Conversely, dopamine receptor sensitivity in the striatum is increased following hypophysectomy.
• The hypophysectomized female rat serves as a valuable model for dissecting the differential roles of the nucleus accumbens septi and striatal dopamine systems in behavior.