Morphine and Intracranial Self-Stimulation in the Hypothalamus and Dorsal Brainstem: Differential Effects of Dose, Time and Site

Abstract

The purpose of this study was to examine if morphine, a drug of abuse, exerts site-specific effects on intracranial self-stimulation (ICSS). Rats, implanted with dorsal brainstem (DB) and hypothalamic (HYP) electrodes, bar-pressed for ICSS at two current intensities eight hours a day during six days each of predrug saline, morphine (2.5, 5.0, 7.5 or 10.0 mg/kg) and postdrug saline conditions. There were three patterns of drug effects: "pure" depressions, "pure" facilitations and a biphasic pattern (depressions followed by facilitations). Repeated morphine administration modified the temporal patterning of these effects: shortened duration of depressions and produced earlier onsets of facilitations. Within an animal, DB electrodes displayed more depressions than the HYP electrodes. Tolerance to the depressant effects, observed frequently, occurred occasionally to the facilitative effects of morphine. The drug effects on ICSS were dissociated from those observed on other behavioral measures, and thus are not artifacts of concomitant changes in activity levels.

Determinants of opioid abuse potential: Insights using intracranial self-stimulation

“…However, after treatment with 3.2 mg/kg/day morphine, morphine produced more robust ICSS facilitation at intermediate brain stimulation frequencies and little or no ICSS depression at higher brain-stimulation frequencies. These results are consistent with other evidence to suggest that repeated morphine administration can produce tolerance to initial ICSS depression and enhanced and accelerated expression of abuse-related ICSS facilitation [10,11,13,14]. The transition from ICSS depression to ICSS facilitation after regimens of repeated morphine treatment is also consistent with clinical evidence that morphine and other MOR agonists often produce dysphoric effects in opioid-naïve humans but euphoric effects in more opioid-experienced subjects [15,16].…”

Ontogeny of morphine withdrawal in the rat.

“…In the adult rat there is also a strong aversive component to opiate abstinence. Adult rats suppress drinking fluids and learn taste aversions (Glick, and, & Charap, 1973; Jackler et al, 1979; Schaefer & Michael, 1983), avoid entering places (Mucha, van der Kooy, O'Shaughnessy, & Bucenieks, 1982; Mucha, 1987), and bury small objects to which they have been exposed during precipitated withdrawal (Mucha, 1991). The results of this study demonstrate only a series of overt behaviors that may constitute a withdrawal syndrome in the infant.…”

Cochlear implantation trough the middle cranial fossa: a novel approach to access the basal turn of the cochlea

“…Jackler & Gladstone 28 used a dissection technique starting in the direction of the medial face (anteriorly to the acoustic pore) toward the lateral portion of the petrous apex to identify the IAM.…”