A research note on some of the critical factors on the dissimilar effects of chlorpromazine and secobarbital on the digit symbol substitution and continuous performance tests.
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Biomedical subjects
Publications and source records attributed to C Kornetsky.
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The effects of orally self-administered ethanol (ETOH) on responding for rewarding brain stimulation were studied. Bipolar electrodes were implanted in either the lateral hypothalamic region of the medial forebrain bundle (MFB-LH) or the ventral tegmental area (VTA) of 6 male F-344 rats. After surgery subjects were trained in a continuous reinforcement procedure (CRF) for constant current rewarding brain stimulation. On alternate days subjects were allowed to drink an ethanol and sucrose solution (12% and 5%, respectively) for 30 min and subsequently tested on the brain stimulation procedure. All subjects showed facilitation of responding (increase in rate) after ingesting low to moderate doses of ETOH (0.4-1.7 g/kg). Depression of responding (decrease in rate) or return to baseline levels (control solution rate) was observed only in those subjects which ingested 2 g/kg or greater during the drinking period. These results indicate that low to moderate doses of self-administered ethanol will increase responding for rewarding brain stimulation. Further, the results suggest that this facilitation of responding is, at least in part, a function of the method of administration and/or the contingent nature of the ethanol delivery (self-administration).
The effects of ethanol on brain-stimulation reward (BSR) were investigated in rats orally self-administering ethanol. Electrodes were stereotaxically implanted in the medial forebrain bundle (MFB) of male F-344 rats. A rate free threshold procedure was used. Animals demonstrated significant threshold-lowering effects after considerable ethanol self-administration experience. To elucidate the significance of the contingent nature of the route of administration in the threshold-lowering effects of ethanol on BSR, a comparison of animals self-administering ethanol to yoked animals receiving it passively through a gastric cannula was made. Significant threshold-lowering effects were only found in the animals self-administering ethanol and not those receiving it noncontingently. Thus, to the extent that brain-stimulation reward is a model of drug-induced euphoria, these results suggest that the reinforcing effects of ethanol are dependent to a greater degree on an interaction between experimental, environmental and pharmacological factors, than other abused drugs.
To characterize the underlying neuroanatomic substrate of morphine (MS) sensitization, changes in the local cerebral metabolic rate for glucose (LCMRglu) were examined in 95 brain regions of male F-344 rats using the 2-deoxy-D-[1-14C]glucose method. The results of these experiments demonstrate that MS-induced sensitization is manifested by increases in basal metabolic activity that last for at least 6 days. Although changes in basal metabolic rate were found to be more extensive in the presence of conditioned cues, the increases in LCMRglu in nonconditioned sensitized rats indicate a basic underlying pharmacologic effect of MS sensitization on basal brain activity. Regions in which MS sensitization had a lasting pharmacologic effect include the shell of the nucleus accumbens, the prelimbic area of the prefrontal cortex, and the dorsolateral prefrontal cortex. Interestingly, the core of the nucleus accumbens and regions of the caudate were found to have an increased LCMRglu only in the presence of conditioned cues, indicating conditioned brain activity without observable changes in behavior. The previous administration of an MS-sensitizing treatment was also found to alter the cerebral metabolic response to a subsequent acute MS challenge (0.5 mg/kg, subcutaneously), most notably in forebrain systems. The more widespread activation of brain structures in the basal state in the presence of conditioned cues suggests that these MS-sensitized rats may model an altered brain state related to craving in the abstinent opiate addict.