Colchicine lesions of ventromedial hypothalamus: effects on regulatory thermogenesis in the rat.

Experiments were carried out to test whether the ventromedial hypothalamus (VMH) is the site of a pathway that stimulates thermoregulatory heat production in brown adipose tissue (BAT). Adult Sprague-Dawley rats received bilateral 50 nl microinjections of colchicine solution into the VMH (0.1, 0.32, 1.0 or 3.2 micrograms per side). Beginning a day later, hyperphagia developed consistently with 0.32 microgram colchicine; and with higher doses there appeared the additional effect that for several days rats developed hypothermia when placed temporarily at 6 degrees C. The degree of hypothermia was limited by activation of nonshivering thermogenesis (NST) in BAT, as evidenced by increased shivering after propranolol injection to block NST, and by increased GDP binding measured in IBAT mitochondria after cold exposure. The findings suggest that chemical lesioning to induce the VMH hyperphagia syndrome does not produce an obligatory impairment of thermoregulation against cold unless the dose of neurotoxin and lesion area extends beyond that which underlies the overeating response. Furthermore, when tolerance to cold is thus compromised, the effect is not readily explained in terms of simply disconnecting a proposed stimulatory pathway from the VMH to BAT.