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At least 127 records · Page 7Linked to original sources
PubMed1998

Drug discrimination studies of the interoceptive cues produced by selective serotonin uptake inhibitors and selective serotonin releasing agents.

MMAI (5-methoxy-6-methyl-2-aminoindan) is a nonneurotoxic, highly selective neuronal serotonin (5-HT) releasing agent. MMAI and other 5-HT releasing agents produce a robust discriminative cue in drug discrimination (DD) studies. The selective serotonin reuptake inhibitors (SSRIs) sertraline and citalopram may also serve as discriminative stimuli, but acquisition of their discrimination required almost twice as much time as for MMAI. In vitro, 5-HT release by MMAI can be blocked by selective SSRIs. However, in the present DD studies, pretreatment with fluoxetine, sertraline, or citalopram 60 min before the training drugs MMAI or (+)-MBDB produced only partial inhibition of the discriminative cue. In substitution tests, sertraline and citalopram partially mimicked the training drugs, whereas only 40% substitution occurred with fluoxetine in MMAI or (+)-MBDB trained rats. In generalization tests, the tricyclic antidepressants imipramine and clomipramine partly substituted for the sertraline, citalopram, and MMAI stimuli. The increase in extracellular 5-HT produced by SSRIs leads to a subtle or feeble drug cue that is apparently difficult for an animal to recognize. This observation contrasts with the 5-HT releasing agents, which clearly produce robust cues that are easily recognized by the animals. However, mechanism(s) responsible for the discriminative stimulus effects of SSRIs and 5-HT releasing agents seem to be similar, at least in part.

3,4-Methylenedioxyamphetamine↗
PubMed1993

Brainstem afferents to the rostral (juxtafacial) nucleus paragigantocellularis: integration of exteroceptive and interoceptive sensory inputs in the ventral tegmentum.

The rostral pole of the nucleus paragigantocellularis (PGi), termed juxtafacial PGi, lies medially adjacent to the facial nucleus and lateral to the pyramidal tract and the nucleus gigantocellularis pars alpha in the caudal ventral pons. This narrow region of the ventral pontine reticular formation is an afferent to the nucleus locus coeruleus, and contains neurons which have been implicated in pain processing, cardiovascular regulation, respiratory control and arousal. Here, we studied brainstem afferents to the juxtafacial PGi using retrograde transport of wheat germ agglutinin-conjugated horseradish peroxidase (WGA-HRP) or of a colloidal gold-protein complex. Anterograde transport of WGA-HRP, or of Phaseolus vulgaris leucoagglutinin (PHA-L), was used to confirm and further detail innervation patterns in the juxtafacial PGi. Results revealed that the juxtafacial PGi receives inputs from a variety of nuclei involved in somatosensory, auditory and autonomic function. Retrograde labeling was prominent in the dorsal column nuclei, the inferior colliculus and the paralemniscal zone of the midbrain, as previously reported in other species. We also found afferents to the juxtafacial PGi that were not previously described, including the paramedian reticular formation and the paraolivary reticular formation. Afferents were also identified from the retrofacial PGi, the caudal medullary reticular formation and the dorsal periaqueductal gray, structures implicated in autonomic and pain regulation. These results indicate that inputs to this subregion of the PGi is distinct from that to the more caudal parts of the PGi, and support the view that the juxtafacial PGi may function in the integration and coordination of polymodal (somatic and visceral) sensory events.

Animals↗
PubMed1996

Studies on the role of 5-HT3 receptors in the mediation of the ethanol interoceptive cue.

The drug discrimination test was used to evaluate the role of 5-HT3 receptors in the mediation of the stimulus properties of ethanol in rats trained to discriminate between ethanol (1.0 g/kg, 10% v/v, i.p.) and saline vehicle. Rats trained to discriminate between a lower dose of ethanol (0.5 g/kg i.p.) failed to attain discrimination criteria after 20 weeks (100 sessions) of training. None of the doses of 5-HT3 receptor antagonists (0.001, 0.01, 0.1, 1.0, 10.0 mg/kg of tropisetron or ondansetron) administered i.p. 30 min before ethanol, antagonized the discriminative stimulus properties of ethanol. Furthermore, none of the centrally (1, 10, 35 micrograms per rat) or i.p. (0.1, 1.0, 2.5, 5.0, 10.0 mg/kg) administered doses of 5-HT3 receptor agonist, 1-(m-chlorophenyl)-biguanide, could replace the ethanol discriminative cue. These results suggest that 5-HT3 receptors are not primarily involved in the mediation of the stimulus properties of ethanol.

Animals↗
PubMed1985

Interoceptive stimuli produced by an anxiogenic drug are mimicked by benzodiazepine antagonists in rats pretreated with isoniazid.

Treatments which increase gamma-aminobutyric acid (GABA) neurotransmission or those which cause stimulation of benzodiazepine receptors, produce anxiolytic effects; but the converse (anxiogenic) effects have not been reported after suppression of either system alone. We report here that simultaneous inhibition of these two systems produces anxiogenic effects. After partial depletion of GABA by isoniazid, the benzodiazepine antagonists, RO 15-1788 and CGS8216, produced pentobarbital reversible anxiogenic effects in the pentylenetetrazol discrimination assay. These results support the hypothesis that GABA and endogenous anxiolytics mutually facilitate modulation of anxiety. They also indicate that there may exist endogenous anxiogenics which act at non-benzodiazepine recognition sites.

Animals↗
PubMed1990

Ethanol interoceptive cue and sleep-time duration in HAS and LAS selectively bred rats.

The drug discrimination paradigm was used to evaluate the effects of selective breeding for differential sensitivity to the hypnotic effects of ethanol. Tenth generation high alcohol sensitive (HAS) and low alcohol sensitive (LAS) rats were trained to discriminate between ethanol (0.6 g/kg, IP) and saline vehicle on a VR-5 schedule of reinforcement. The animals were tested with 0.15, 0.3, and 0.9 g/kg ethanol following 40, 50, and 60 training sessions. Sleep-time, tested before and following discrimination training, did not change for the HAS and LAS animals. Dose-response functions showed differences between the HAS and LAS phenotypes after 40 training sessions but not after 50 sessions or after 60 sessions.

Animals↗
PubMed1989

Environmental and interoceptive influences on chronic low back pain behavior.

The operant conditioning theory states that environmental stimuli greatly influence chronic pain behavior. In contrast, the hypochondriasis theory states that pain behavior is the result of an intensified pain perception which is part of a more general augmentation and amplification of normal bodily sensations. The operant theory predicts that pain behavior (operationalized as poorer endurance on the part of chronic low back pain patients as compared to the endurance of control subjects in a series of 6 working-to-tolerance treadmill tests) will decrease when no verbal or non-verbal feedback for treadmilling behavior is given. This hypothesis could not be confirmed in the present study. The hypochondriasis theory predicts that chronic pain patients will report more bodily sensations, both at rest and after treadmill exercises. This hypothesis was strongly supported by the findings of the present study.

Adult↗
PubMedDate not supplied

Ethanol-produced interoceptive stimuli are time dependent in selectively bred HAS and LAS rats.

Fourteenth generation high alcohol-sensitive (HAS) and low alcohol-sensitive (LAS) rats were trained to discriminate the effects of 600 mg/kg intraperitoneally administered ethanol from its vehicle at 6 and 30 min postadministration. Each of the earlier- and later-trained animals were given lower doses of ethanol and ED50 values at their trained postadministration interval were found to be nonsignificantly different. Thus, there was no difference between HAS and LAS animals as to their sensitivity to the discriminative effects of ethanol. Phase-generalization studies, where rats trained at 6 min postadministration were tested with the drug at 30 min postadministration were shown not to generalize, whereas the animals trained at 30 min postadministration and tested at 6 min postinjection were shown to readily discriminate the discriminative stimuli. This asymmetrical generalization lends evidence to the biphasic action of ethanol, and suggests that the earlier phase is quantitatively different than the latter phase. The similarity in sensitivity of the LAS and HAS animals, furthermore, suggests that the discrimination of ethanol is not based on its hypnotic effects.

Animals↗
PubMed2005

A new focus on interoceptive properties of adrenal medulla.

The adrenal medulla is an important part of the sympathoadrenal system. Chromaffin cells of the adrenal medulla respond to a broad spectrum of stressful situations by releasing epinephrine and norepinephrine. Originally, it was accepted that this response is controlled exclusively by central nervous system structures. However, it was also demonstrated that a surgically denervated adrenal medulla can respond directly by secreting epinephrine and norepinephrine during an imbalance of internal environment (hypoglycemia, asphyxia). Published data had documented the innervation of the adrenal medulla by sensory neurons of spinal dorsal root ganglia. In addition, recent data showed that ganglion cells of the adrenal medulla project ascending axons. These data suggested potential transmission of information from the adrenal medulla to the central nervous system regarding metabolic changes in the blood. This paper presents an overview of possible involvement of adrenal medullary chromaffin cells in the detection of changes in the internal environment and in the transmission of this information to the central nervous system.

Adrenal Medulla↗
PubMed2005

Stimulus gated cocaine sensitization: interoceptive drug cue control of cocaine locomotor sensitization.

Repeated cocaine treatments typically generate sensitization effects which are environment specific. In this study, we investigated whether drug treatments with highly selective receptor specificity can also function as contextual cues to control the expression of cocaine sensitization effects. Two experiments were conducted in which separate groups of rats (N=10) received ten paired or unpaired cocaine (10.0 mg/kg) treatments. In the experiments, autoreceptor preferring low doses of either the 5-HT1A agonist, 8-OHDPAT (8OH) (0.05 mg/kg) or the D1/D2 agonist apomorphine (APO) (0.05 mg/kg) were administered 20 min prior to cocaine administration and test environment placement (paired treatment). Under these conditions, the drug cues generated by the 8OH/APO treatments were associated with the cocaine stimulant effect in the test environment. The unpaired treatment groups received the same drug treatments but the cocaine was administered after testing, in the homecage. Consequently, for these groups, the 8OH/APO drug cues generated by the drug treatments would not become associated with the cocaine stimulant effect in the test environment. Critically, both 8OH and APO pretreatments elicited equivalent unconditioned response effects which were opposite to the cocaine unconditioned response effects; that is, behavioral inhibition vs. behavioral stimulation. Initially, the 8OH and APO pretreatments prevented the locomotor stimulant effects of cocaine; but, these inhibitory effects were reversed in the paired groups with repeated cocaine treatments, consistent with the emergence of cocaine sensitization effects. In the unpaired 8OH and APO pretreatment groups, behavioral suppression persisted throughout the treatment protocol. Subsequently, paired and unpaired groups were compared in four conditioning/sensitization tests. The conditioning tests included: a saline/saline test; and a 8OH/saline test (Experiment 1); and, a saline/saline test and a APO/saline test (Experiment 2). There were no paired/unpaired group differences in these conditioning tests. The sensitization tests included: a saline/cocaine test; and a 8OH/cocaine test (Experiment 1); and, a saline/cocaine test and a APO/cocaine test (Experiment 2). There were no paired/unpaired group differences in the saline/cocaine test for sensitization but paired/unpaired group differences were found in both the 8OH/cocaine and APO/cocaine sensitization tests. In these tests the paired but not the unpaired groups exhibited cocaine locomotor sensitization effects. Critically when, in an additional test, the pretreatments in the cocaine tests were reversed (i.e., 8OH paired group received APO and APO paired group received 8OH prior to cocaine), then there was no evidence for cocaine sensitization. Since the 8OH/APO pretreatments had equivalent inhibitory response effects, it was the stimulus properties of these drugs which controlled the expression of the cocaine locomotor sensitization effects. These findings support the critical role of associative processes in the stimulus-gating of psychostimulant drug sensitization. Importantly, this report incorporates a new methodology in which context can be specified in terms of highly specific brain receptor targets rather than in terms of global environmental situational cues.

8-Hydroxy-2-(di-n-propylamino)tetralin↗
PubMed2001

Reactivity to interoceptive cues in nocturnal panic.

In this study, patients with panic disorder (PD) who suffered nocturnal panic (NP) attacks were compared with PD patients who never experienced NP attacks and healthy controls. Three tasks were chosen to evaluate attention to cardiac cues, reactivity to induction of respiratory cues, and reactivity to relaxation cues. Relative to healthy controls, PD groups reported more fear of all three tasks and showed more physiological arousal in response to the hyperventilation task. The only task on which the two PD groups differed was the relaxation task, where nocturnal panickers were significantly more distressed. These findings are consistent with the notion that nocturnal panickers are fearful of states involving a diminution of conscious awareness or vigilance.

Agoraphobia↗
PubMed2001

Social phobic interoception: effects of bodily information on anxiety, beliefs and self-processing.

It has been suggested that body-state information influences self-perception and negative thinking in social phobia [Clark, D. M., & Wells, A. (1995). A cognitive model of social phobia. In R. G. Heimberg, M. R. Liebowitz, D. A. Hope & F. R. Schneier (Eds.), Social phobia: diagnosis, assessment and treatment (pp. 69-93). New York: Guilford Press.]. This study explored the effects of body-state information on anxiety and cognition in patients with generalised social phobia during a feared social interaction. It was hypothesised that information concerning an increase in pulse rate would lead to increments in anxiety, negative beliefs and self-processing whilst information concerning a decrease in pulse rate would have the opposite effect. The results of this study were generally consistent with the hypotheses. These findings are important as they may help to account for fluctuations in anxiety, negative beliefs and self-processing in social situations that do not present objective social threat. In particular, social anxiety appears to be modulated by body-state information. The implications of the present findings for cognitive therapy of social phobia are briefly discussed.

Adolescent↗