Date of Award

1974

Degree Type

Thesis

Degree Name

Master of Science in Pharmacology and Toxicology

Department

Pharmacology and Toxicology

First Advisor

Harbans Lal

Abstract

The present investigation was undertaken to demonstrate how a conditional stimulus (cs) similar to the action of morphine, can increase rectal temperature during morphine abstinence. Also, the study implicates certain neurotransmitters which are involved in the ef'f'ect of conditional stimulus and of morphine to affect rectal temperature. Rats were given two equally spaced injections of morphine sulfate daily, each injection being paired with a bell. The bell was presented for one minute and the injection was given during the last 15 seconds. This procedure was followed for lJ-15 days. Twenty-four hours after the last injection the bell was presented alone. The rats learned to increase their body temperature following the presentation of the bell. This increase was specific only to animals that had the bell paired with morphine prior to challenge treatment. This change in temperature was shown to be approximately equivalent to an injection of 12.5 mg/Kg at 24 hr after the last morphine injection. When naive animals were exposed to a bell, no change in temperature was observed. Those rats which had received a random bell or no bell during addiction demonstrated no change in temperature when presented with the CS 24 hr after the last injection. Naloxone, a narcotic antagonist, produces hypothermia in normally addicted rats only if given within 12 hr after the last morphine injection. In contrast, when administered to CS-morphine paired animals which received only the CS 24 hr after the last morphine injection, naloxone caused a hypothermia. This data suggest that the CS and morphine are working by either the same or parallel pathways in the brain. The CS induced increase in temperature was blocked during withdrawal ~hen t h e animals were pretreated with phenoxybenzamine (2 mg/Kg ), mecarnylamine (2.5 mg/Kg) , haloperidol (0. 2 mg/Kg) and benztropine (0 . 625 mg/Kg ) but was not blocked by cyproheptidine (2 mg/Kg). Morphine induced increase in temperature was blocked by mecamylamine, phenoxybenzamine and cyproheptidine but was not blocked by haloperidol or bentropine. Propranolol (2 mg/Kg ) had little effect on the increase in temperature due to the CS or morphine when given at 24 hr after the last CS-morphine pairing. The CS was not able to affect other withdrawal symptoms such as shakes, ptosis, piloerection, loss in body weight, or writhing when presented 24 hr after the last morphine. These data indicate that the increase in temperature elicited by morphine during withdrawal can be classically and central nervous system.

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