PubMed · 5658914
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J M Telford, P F Coville. 1968-06-08. Drugs and hyperthyroidism.. https://doi.org/10.1136/bmj.2.5605.624-c
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Distribution of cocaine- and amphetamine-regulated transcript-like immunoreactivity (CART-LI) was studied in the rat spinal cord, sympathetic ganglia and adrenal glands by immunohistochemical methods, utilizing a polyclonal antiserum raised against the CART peptide fragment 55-102. CART-LI was detected in nerve fibers and in basket-like terminals surrounding many postganglionic neurons of the superior cervical ganglion (SCG), stellate, paravertebral and prevertebral ganglia. Postganglionic neurons exhibited low or non-detectable levels of CART-LI. Surgical sectioning of the cervical sympathetic trunk for 6-7 days resulted in a nearly complete loss of CART-LI fibers and terminals in the SCG. In the adrenal gland, CART-LI nerve fibers formed a plexus underneath the capsule, some of which bifurcated and made a sharp turn toward the adrenal medulla, where clusters of chromaffin cells were intensely labeled. The detection of CART-LI in sympathetic ganglia and adrenal glands extends the previous observation of the presence of CART-LI in sympathetic preganglionic neurons and further supports the notion that CART peptide(s) may function as a signaling molecule in the sympatho-adrenal axis.
Converging evidence supports a role for cholecystokinin (CCK) in modulating dopamine (DA)-mediated activity in the rat mesolimbic system. In particular, CCK co-localized with mesolimbic DA cells originating in the ventral tegmental area potentiates DA function in the medial posterior nucleus accumbens (mpNA) through CCK-A receptors. Recently, a strain of rats lacking the CCK-A receptor, Otsuka Long Evans Tokushima Fatty (OLETF), has been discovered making it possible to study the mesolimbic DA regulatory role of CCK-A receptors. Previous studies have shown that OLETF rats are less sensitive to amphetamine (AMPH)-induced behavioral effects compared to controls. To determine if this altered sensitivity is associated with decreased AMPH-induced postsynaptic activation in the mpNA in OLETF rats, we performed the following experiment. OLETF (CCK-A mutants) and Long Evans Tokushima Otsuka (LETO) rats (controls) were given subcutaneous injections of either saline or AMPH (5.0 mg/kg). One hour after injection all animals were sacrificed and activation of the mpNA was assessed using in situ hybridization with antisense probes for zif268 mRNA. AMPH treatment produced a significant up-regulation of zif268 mRNA expression in both OLETF and LETO rats (P</=0.0002), compared to saline treatment. However, AMPH had almost an identical effect on zif268 mRNA expression in the mpNA in both rat strains suggesting similar postsynaptic neural activation. The significance of this AMPH-induced zif268 mRNA expression in these two rat strains and its relationship to CCK function in the nucleus accumbens are discussed.
Genetic predisposition and environmental factors such as perinatal complications are believed to contribute to the etiology of schizophrenia, a disorder involving enhanced CNS dopaminergic activity. This study used a rat model to test whether genetic factors and a minor birth complication, i.e. Caesarean section (C-section) birth, interact in producing longterm effects on dopamine-mediated behavior. For this, we compared the effects of vaginal and C-section birth on amphetamine (AMPT)-induced locomotor activity in strains of rats differing in genetic composition. In Sprague-Dawley rats, C-section birth increased AMPT-induced locomotion compared with vaginal birth. By contrast in Lewis rats, C-section birth reduced AMPT-induced locomotion compared with vaginal birth. In Fischer rats, AMPT-induced locomotion was increased by C-section under maternal anesthesia but decreased by C-section after maternal decapitation, compared with vaginal birth. It is concluded that a minor birth complication like C-section can have differing long-term effects on dopaminergic function in the rat, depending on the genetic composition of the individual.