The destruction of ascending noradreniergic pathways by bilateral microinjections of 6-hydroxydopamnine made laterally to the pedunculus cerebellaris superior completely abolished the in vitro synthesis of [(3)H]norepinephrine from L-[(3)H]tyrosine in slices and in synaptosomes of the rat cortex. However, normal [(3)H]dopamine synthesis could still be observed in both cortical preparations from animals with lesions. These results provide the first biochemical support for the existence of dopaminergic terminals independent of noradrenergic terminals in the rat cortex.
The aim of the present study was to assess the influence of experiential factors on the vulnerability of rats to develop amphetamine (AMPH)- and stressor-induced behavioral sensitization. Young male Wistar rats with previous social experience were isolated from their peers for 2 weeks. 1) The effect of this short-lasting social deprivation were: a) a reduced tendency to explore a fearful environment; b) a prolonged exploratory activity in response to a novel but little fearful environment; and c) a dose-dependent increase in the psychomotor stimulation induced by systemic AMPH injection. 2) After repeated AMPH injections (injection every other day for 10 days), isolated rats exhibited behavioral sensitization at lower doses (0.5 and 0.75 mg/kg) than those required for group-housed rats (1 mg/kg). 3) After being submitted to a repeated stressor (3, 7 or 14 footshock sessions, with 2 days between sessions), the isolated rats exhibited a greater increase in the behavioral responsivity to a subsequent AMPH challenge (1 mg/kg) than did the group-housed rats regardless of the number of stress sessions. In conclusion, these results suggest that experiential factors such as privation of contact with peers (social isolation) may make rats more vulnerable to the long-term repercussions of chronic environmental and pharmacological challenges.
,-Endorphin in nanomole quantities produced a stimulation of locomotor activity when infused into the region of the dopamine cell bodies of the ventral tegmental area (VTA) in rats. a-, -y-, and des-Tyr-y-endorphin produced similar effects, but the D-alanine analogues of a-and y-endorphin produced a larger and longer-lasting activation, presumably reflecting their resistance to degradation. This locomotor activation was reversible by pretreatment with naloxone and b destruction of the terminal projections of the mesocorticolimzic dopamine system originating in the VTA. These results demonstrate that locally infused endorphin can interact with the opioid receptors in the VTA, and they suggest a means by which endorphins activate limbic excitability. The identification and localization within the central nervous system of endogenous peptides with opiate-like actions suggested that these substances may act as central neurotransmitters (1, 2). Both [Metlenkephalin [/3-lipotropin-(61-65)] and f3-endorphin (3-END) [/3-lipotropin-(61-91)] exhibit opiate-like activity when injected into the ventricles (3, 4). These effects have included analgesia, catatonia, loss of corneal and tail pinch reflexes, and wet-dog shakes (3), and :3-END appeared to be more potent than [Met]enkephalin (5-7). In addition, most of these effects are reversible by naloxone. These preliminary results suggested to some that-the endorphins could be an etiological factor in mental illness (3,8), but the nature and specification of this action remains to be determined.Opiate receptors and enkephalin-like peptides have been found in the region of the ventral tegmental area (VTA) (9), and in at least some accounts receptors appear to be localized on mesolimbic dopamine neurons (9, 10). These mesolimbic dopamine neurons are thought to be involved in the locomotor stimulation produced by psychomotor stimulants (11, 12) but also may have a role in general activation and the actual organization of behavior (13,14). In fact, some authors have suggested that the activation of the mesolimbic dopamine system may be an important model of schizophrenia (15). This intriguing similarity of the putative function for the mesolimbic dopamine system and the endogenous opiate systems requires further analysis of their interaction at the behavioral level, and our initial studies have concentrated on the activation of the mesolimbic dopamine system as measured by simple locomotor activity.Recent work has demonstrated that morphine and [D-Ala2, Met]enkephalin when injected into the VTA can produce significant increases in locomotor activity that may reflect an activation of these mesolimbic dopamine neurons (16,17). The purpose of the present study was to determine whether 1-END also interacts with the opiate receptors in the VTA to produceThe publication costs of this article were defrayed in part by page charge payment. This article must therefore be hereby marked "advertisement" in accordance with 18 U. S. C. §1734 solely to indicate this fact. 2323 locomot...
In the absence of any active intervention, the place aversion produced by opiate withdrawal is very long lasting and provides a model for protracted abstinence that may be useful for delineating the neurobiological substrate for vulnerability to relapse.
Adult male rats submitted to mild, 20 min electric foot shock sessions for 10 days displayed an enhanced locomotor response to 0.75 mg/kg (+)amphetamine 24 h after the last shock session, when compared to non-stressed controls. This effect was still present in rats specifically deprived of their forebrain noradrenergic innervation, suggesting the involvement of a dopaminergic mechanism. Cortical and limbic dopamine turnover which increased immediately after acute and repeated foot shocks returned to normal 24 h later, at the time of the pharmacological testing. This fact indicates that a permanent modification of the basal DA activity is not responsible for the above effect of stress. Locomotor hyperactivity produced by 0.6 mg/kg apomorphine was enhanced in experimental animals, while hypoactivity resulting from the injection of 0.05 mg/kg apomorphine was similar in control and shocked rats. This latter result suggests the existence of an increased postsynaptic DA sensitivity as a result of repeated stress.
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