THE INFLUENCE OF THE ADRENAL GLANDS ON RESISTANCE : I. THE SUSCEPTIBILITY OF ADRENALECTOMIZED RATS TO MORPHINE.

1. The majority of rats (Mus norvegicus), because of accessory cortical tissue, will survive double adrenalectomy indefinitely under optimum conditions. 2. Resistance to morphine is greatly diminished in healthy adrenalectomized rats tested before hypertrophy of the accessories occurs. 3. This greater sensitiveness seems to be due to some fundamental alteration in metabolism dependent on a partial adrenal insufficiency. Protocol 1.—Rat 13; brown and white, male. Sept. 15, 1922. In stock. Sept. 18. Active, vigorous, and very vicious. Weight 281 gm. Operation, double adrenalectomy. Prompt recovery. Sept. 21. Very active and vicious. Sept. 22. Jumps viciously this morning on opening the cage. This afternoon, quiet and marked diarrhea. Transferred to individual cage. Eating nothing. Sept. 23, Diarrhea. Quiet, Sept. 24. Diarrhea diminished, more active, but is not vicious. Appetite poor, ate 5 gm, Sept. 25. Diarrhea, ate nothing. Sept. 26. Diarrhea still marked, ate nothing. Died this afternoon. Autopsy.—Weight 215 gm. Thyroid, heart, and lungs normal. Abdomen: intra-abdominal fat almost completely gone. Adrenals absent. Stomach: definite multiple minute hemorrhages in the mucous membrane throughout the pyloric part. Intestines: several loops of small gut deep red in color. Liver: nutmeg color. Protocol 2— Rat 43; white, male. Oct. 20, Active. Weight, 236 gm. Operation, excision of right adrenal and excision of piece of pancreas near left adrenal. Moderate bleeding. Oct. 22. Has not eaten since operation. Oct. 23. Active, beginning to eat. Oct. 27. Active,, eating well now. Slight diarrhea. Weight, 222 gm. At 11:10 a.m. injected subcutaneously with 1.78 cc. of 1 per cent morphine sulfate solution ( = 80 mg. per kg.). 1:30 p.m., quiet. 6 p.m., recovering. Oct. 28. Active, eating well. Nov. 10. In good condition. Sacrificed Jan. 8. Right adrenal absent, left adrenal intact. Protocol 3.— Rat 42; white, male. Oct. 20, Active. Weight, 320 gm. Operation, excision of both adrenals, much abdominal fat. Oct. 21. Ate 10 gm. of food. Oct. 22. Active, ate all of food (15 gm.). Oct. 27. Active. Weight, 310 gm. At II a.m. injected subcutaneously 0.62 cc. of 1 per cent morphine sulfate solution (= 20 mg. per kg.). 1:30 p.m., marked pilomotor effect. Did not move. 6 p.m., very quiet. Oct. 28. Very quiet, not eating. Oct. 29. Quiet. Ate a little today. Oct. 30. Very dull, not eating. 5 p.m., comatose. 9:30 p.m., found dead. Autopsy.—Weight 277 gm. Diarrhea. Thyroid large and dark red. Heart and lungs normal. Abdomen: scant fat. Both adrenals absent. No accessories seen. Right testicle congested. Liver and spleen normal. Stomach: one hemorrhage beneath mucosa near fundus. Prolocol4.—Rat 21;white and brown,male. Sept-27. Active. Weight345gm. Operation, excision of left adrenal, easy operation. Oct. 4. Active, eating well. Weight 333 gm. At 10:48 a.m. injected 0.75 cc. of 2 per cent morphine sulfate intravenously ( = 45 mg. per kg.). 10:50 a.m. respirations imperceptible. Board-like rigidity. 11:10 a.m. respirations very shallow. Complete coma. 1 p.m. condition gradually improving. Oct. 5. Alert and active, eating well. Oct. 11. Active, eating well (15 gm. per day). Weight 335 gm. Operation, excision of right adrenal. Easy operation, no hemorrhage. Moderate fat. Oct. 18. Excellent condition, active, good appetite. Weight 321 gm. At 3:50 p.m. injected 0.74 cc. of 1 per cent morphine sulfate intravenously ( = 23 mg. per kg.). 3:52 p.m. respirations imperceptible for a minute, and rat is stiff. 3:57 p.m. voluntary movement. Oct. 19. 9 a.m. very quiet. Marked ruffling of fur. Not eating. 6 p.m. very quiet and dopey. Oct. 20. Found dead this morning. Autopsy.—Well preserved fat. Diarrhea. Thyroid rather large and red. Heart and lungs normal. Abdomen: both adrenals absent. No accessories seen. Stomach: five distinct hemorrhages into mucous membrane, one is 3 x 4 mm. Protocols 5.—Rat 24; white and gray, male. Sept. 27. Active. Weight 320 gm. Operation: double adrenalectomy. Easy operation. Sept. 29. Eating well, alert. Oct. 2. Active, ate 12 gm. Weight 318 gm. Oct. 3. Ate 10 gm. Oct. 4. Active. Weight 311 gm. Ate 12 gm. At 10:30 a.m. injected 0.28 cc. of 1 per cent morphine sulfate intravenously (= 9 mg. per kg.). Became quiet but did not stop breathing. 5 p.m. quiet and fur ruffled. Oct. 5, very quiet. Eyes closed most of time. Hunched up, fur ruffled. Drinks with eyes closed. Not eating. Oct. 6. Head between front paws most of time. Pilomotor reaction marked. Oct. 7. Condition about the same. Has eaten nothing since operation. Oct. 8. Seems slightly more active, not eating. Oct. 9. Ate 5 gm. of food, first since injection. Oct. 10. Very drowsy. Stools firm and white. Not eating. Oct. 14. Very weak. Has not eaten 10 gm. since injection. Oct. 15. Found dead this morning. Autopsy.—Weight 240 gm. Thyroid moderate size. Heart in systole. Lungs normal. Abdomen: adrenals absent. No accessories seen. Left testis converted into a sack filled with dark red grumous material. Right testis atrophied. Stomach: postmortem change.