At a Detroit research program from 2004 to 2005, out-of-treatment chronic daily heroin users (N = 100) were interviewed to evaluate relationships between past 30-day income and factors influencing heroin price, expenditures, and consumption. Weekly heroin purchasing frequency was positively related to income and number of suppliers, and negatively related to time cost (min) from primary supplier. Daily heroin consumption was positively related to income and injection heroin use, and negatively related to unit cost of heroin. Implications and limitations are noted. Simulations are underway to assess within-subject changes in drug demand. Supported by NIH/NIDA R01 DA15462 and Joe Young, Sr. Funds (State of Michigan). 相似文献
The aim of this study is to analyze further the opioid receptor subtypes involved in the augmentation of behavioral activity
after dopamine depletion in the nucleus accumbens of rats. Initially, the opioid receptors involved in the augmentation of
locomotion produced by endogenous opioids were evaluated by microinjection of kelatorphan, an inhibitor of proteolytic enzymes
that inactivates enkephalin, with or without specific antagonists forμ1 orδ-opioid receptors, naloxonazine or naltrindole, respectively. Kelatorphan produced a dose-dependent increase in horizontal
photocell counts and vertical movements. At all doses examined the behavioral response was augmented in rats sustaining accumbal
dopamine lesions. The augmentation in dopamine-depleted rats was partially blocked by naloxonazine or naltrindole. Since the
motor stimulant response to intra-accumbens microinjection of theδ-opioid agonist, [d-penicillamine2,5]-enkephalin, was not augmented in a previous study, we tested the behavioral response to a new endogenousδ-opioid agonist, [d-Ala2] deltorphin I. The locomotor response to deltorphin was slightly augmented in dopamine-depleted rats. These data suggest
that the augmentation in the motor response elicited by endogenous opioids after dopamine lesions in the nucleus accumbens
involves bothμ1 andδ-opioid receptors. 相似文献
The identification of useful new drugs, when not due entirely to serendipity, has often relied on in vivo techniques that are both difficult to interpret and to perform. The receptor binding technique, however, by allowing the direct study of the specific biochemical site of action of most psychotherapeutic drugs has provided a simple, selective, and sensitive method to study drug-receptor interactions. The biochemical locus of action for a family of drugs can often be identified by comparing their absolute potencies in in vivo systems with their affinities at a number of drug and/or neurotrans mitter receptor binding sites. Once a particular binding site is identified as therapeutically relevant, affinity for this binding site can be used as a screen for novel compounds that may show similar in vivo activity. Detailed structure-activity relationships can be determined in vitro without the problems of metabolism and differential absorption that complicate in vivo studies. Such studies allow the pinpointing of active sites within the drug molecule for further synthetic manipulations. Receptor binding studies have been essential in the elucidation of the therapeutic mechanisms of neuroleptics, tricyclic antidepressants, opiates, and benzodiazepines. Receptor binding studies are not only useful in the identification and quantification of therapeutically useful drug receptor interactions but have also been invaluable in the study of similar interactions that manifest themselves as drug-induced side effects. Such studies may eventually allow the development of drugs that are not only more therapeutically potent but are also free of side effects. Radioreceptor assays have also been introduced to measureserum drug levels of neuroleptics, antidepressants, anticholinergics, benzodiazepines and P-adrenergic antagonists. These methods have the advantage of being quick, sensitive, selective, and inexpensive. 相似文献
Interleukin-1 (IL-1) exerts a wide variety of biological effects on various cell types and may be regarded as a pleiotropic peptide hormone. Biological evidence suggests that IL-1 participates in the modulation of central nervous system physiology and behaviour in a fashion characteristic of neuroendocrine hormones. In this investigation, recombinant (r) human (h) IL-1 and r mouse (m) IL-1 were examined for their modulation of opioid peptide receptor binding in vitro. Experiments were performed on frozen sections of rat brain. Receptor binding of radiolabeled substance P and of radiolabeled neurotensin were not significantly affected by the presence of rIL-1s. Recombinant IL-1s, however, significantly enhanced specific binding of 125I-beta-endorphin (125I-beta-END) and of D-ala2-(tyrosyl-3,5-3H)enkephalin-(5-D-leucine) (3H-D-ALA), equipotently and in a concentration-dependent manner with maximal activity occurring at a concentration of 10 LAF units/ml. The increased binding of 125I-beta-END and 3H-D-ALA was blocked steroselectively by (-)-naloxone and by etorphine, suggesting detection of opiate receptors. In addition, brain distribution patterns of receptors labeled in the presence of rIL-1s corresponded to patterns previously published for opiate receptors. Autoradiographic visualization of receptors revealed that rIL-1s in the different areas of the brain exert their effect on opioid binding with comparable potencies. The data suggest that certain central nervous system effects of IL-1s may be mediated by their selective interaction with opiatergic systems at the receptor level.(ABSTRACT TRUNCATED AT 250 WORDS) 相似文献
1. 1. Humans and laboratory animals given access to opiate and stimulant drugs frequently become compulsive users of these drugs, and often, in spite of prolonged periods of abstinence, persist in drug-seeking behavior and relapse to drug-taking. Evidence suggests that such drugs act on positive appetitive systems of the brain to maintain drugtaking and that, in the absence of drugs, stimuli previously associated with the drug state might acquire the ability to arouse motivational states similar to those activated by the drugs themselves.
2. 2. In rats previously trained to self-administer cocaine or heroin intravenously, noncontingent ‘priming’ intravenous infusions of cocaine or heroin lead to reinstatement of drugtaking behavior. Priming infusions of pharmacologically related drugs and drugs with similar stimulus properties also reinstate responding.
3. 3. Application of morphine to the cell body region of dopaminergic neurons of the ventral tegmental area (VTA), a site known to support morphine self-administration, reinstates both heroin and cocaine self-administration behavior. Reinstatement is blocked by pretreatment with naltrexone. Morphine applied to several other brain areas rich in opiate receptors does not reinstate the behavior.
4. 4. Application of morphine to the VTA, a site known to support conditioned place preferences as well as self-administration, causes increased locomotion that is naloxone reversible. This locomotor activity shows sensitization upon repeated administration; an effect that is specific to the environment in which morphine is administered. Conditioned increases in activity are observed in the same environment. Neither conditioning nor sensitization develops when animals are pretreated with pimozide.
5. 5. These findings support the view that, opiates and stimulants are administered because of their effects on positive appetitive systems of the brain and that, through conditioning, stimulus events that are associated with these positive appetitive actions of opiates and stimulants acquire the ability to elicit neural states that mimic aspects of those elicited by the drugs themselves. The arousal of these states may act to reinstate (facilitate relapse) and to maintain drug-taking behavior. This positive incentive account of compulsive drug-taking and relapse differs from the ‘drive-reduction’ view that continued drug use depends primarily on efforts to reduce or avoid symptoms of withdrawal, and that conditioned stimuli associated with drugs can initiate and maintain drug-taking behavior through the elicitation of withdrawal-like, drug-opposing, conditioned responses.
1. Both naloxone, an opiate antagonist, and levorphanol, an opiate agonist, inhibit the enhanced renal response to aldosterone produced by both ?-dopa pretreatment and a high K+ diet. 2. This supports the evidence for a common mechanism of action for the enhancement of the renal response to aldosterone produced by ?-dopa and a high K+ diet. Whether this mechanism is dopaminergic or opiate is uncertain. 3. The inhibition of the enhanced response, produced by ?-dopa, by opiates is consistent with previous findings of displacement of 3H-dopamine from renal homo-genates by opiates and supports the hypothesis that the binding sites relate to the renal response to aldosterone. 相似文献
Intracerebroventricular (ICV) injection of both enkephalin (100 micrograms) and morphine (200 micrograms produces characteristic electrographic seizures. Injection of low doses of either morphine or levorphanol into the lateral ventricle of the brain prior to the administration of epileptogenic doses of enkephalin can block the induction of such seizures. A similar trend was observed when either opiate preceded ICV morphine. Microinjections of both morphine (30 micrograms) or levorphanol (40 micrograms) into the periaqueductal gray area (PAG) or into the nucleus accumbens resulted in potent analgesia. However, only morphine injected into the nucleus accumbens was effective in blocking electrographic seizures induced by ICV enkephalin. On the basis of this and other previous findings we propose that the excitatory-epileptic and the inhibitory-antiepileptic action of opiates and opioids are mediated by two different systems. Furthermore, we propose that such systems may differ both in their anatomical distribution and in the classes of opiate receptors underlying their action. 相似文献