Compulsive Gnawing in Rats After Implantation of Drugs Into the Ventral Thalamus. A Contribution to the Mechanism of Morphine Action

Abstract

1Implantation of morphine into various parts of the corpus striatum of rats evokes only weak gnawing responses. 2 Deposition of apomorphine, morphine or methadone in the region of the nucleus ventralis thalami produces a biphasic response, i.e. general excitation, followed by a period of intense gnawing.3 The effect of both apomorphine and morphine is blocked by chlorpromazine, haloperidol and pimozide. However, pretreatment with ca-methyltyrosine methyl ester or a-methyldopa prevents only the gnawing response to morphine, but not to apomorphine. 4 Systemic nalorphine, morphine or pethidine suppress the gnawing response, evoked by thalamic implants of apomorphine or morphine. 5 Systemic amphetamine potentiates the effect of thalamic deposits of morphine. 6 Compulsive gnawing, following implantation of morphine into the ventral region of the thalamus, probably results from enhanced production and release of catecholamines.

Female rats consume and prefer oxycodone more than males in a chronic two-bottle oral voluntary choice paradigm

“…Gnawing and other oral stereotyped behaviors can be induced by repeated high doses of morphine (Wennemer and Kornetsky, 1999) or by stress and are mediated by endogenous opioids (Bergmann et al, 1974;Ernst and Smelik, 1966;Morelli et al, 1989) . One source of stress in the two-bottle choice model is social isolation which reduces tolerance to morphine but also precipitated withdrawal (Broseta et al, 2005;Coudereau et al, 1996;Jiménez and Fuentes, 1993) .…”

“…Moreover, because social isolation is more stressful for females than males (Beery and Kaufer, 2015;Hatch et al, 1965;Westenbroek et al, 2005) , the increased gnawing in particular by experimental females may be explained by an opioid-mediated activation of the dopaminergic mesolimbic system known to induce gnawing behavior (Bergmann et al, 1974;Morelli et al, 1989) . : appetitive and reinforcing behavior, escalation, and incentive salience.…”