PubMed · 4172781
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1968-06-08. Amines, alerting, and affect.. https://pubmed.ncbi.nlm.nih.gov/4172781/
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RATIONALE: The anxiogenic DMCM, an inverse benzodiazepine agonist, was used to explore the relationship between negative affective states and pain. Past work suggests that the outcome obtained may depend on both the intensity of the affective state and the way in which pain is inferred. OBJECTIVES: The present study was designed to test the impact of relatively low doses of DMCM on multiple measures of pain reactivity and learning. METHODS: In experiment 1, systemic injections of 0.00, 0.015, 0.06, and 0.25 mg/kg DMCM were administered before vocalization and tail movements were assessed in response to a gradually incremented shock and radiant heat stimulus. Experiment 2 tested the effects of DMCM on Pavlovian conditioning. DMCM-treated subjects experienced a context paired with an aversive unconditioned stimulus (US) and conditioned freezing was assessed the next day. RESULTS: Experiment 1 showed that DMCM inhibits both a spinal nociceptive reflex (tail-flick to heat) and a supraspinal measure of pain (vocalization to shock). Because these inhibitory effects could reflect a disruption in motor function, experiment 2 employed a remote test based on Pavlovian conditioning. A moderate dose of DMCM undermined learning, implying that the drug decreased the affective impact of the aversive US. CONCLUSIONS: DMCM induces hypoalgesia on a wide range of assays. Furthermore, pharmacologically inducing a negative affective state blocks Pavlovian fear conditioning. It is suggested that DMCM induces a state of panic and that this state inhibits pain.
RATIONALE: Recent reports suggest the possible efficacy of selective serotonin reuptake inhibitors (SSRIs) in treating particular symptoms of Huntington's disease (HD), such as aggressiveness and agitation. However, predictive features to identify HD subjects who may benefit from this treatment have not been established. OBJECTIVES: Two individuals from a large HD pedigree with a very high prevalence of obsessive-compulsive disorder (OCD) have been treated with fluoxetine, an SSRI. We aimed at testing whether the co-occurrence of the two disorders in this pedigree might have some underlying pathogenic similarities, maybe also resulting in a good response of HD symptoms to the anti-obsessional drug fluoxetine. METHODS: Each patient was evaluated, started on fluoxetine treatment, and then reassessed monthly with: (a) the HD motor rating scale, to rate the impairment of movement, and (b) the mini mental state examination, for a cognitive ascertainment. They had a complete psychiatric and neurologic examination as well. RESULTS: Both subjects showed an excellent response to fluoxetine. One patient exhibited improvement of the motor and behavioral components of the disorder, while the other improved also in the cognitive domain of HD. The best response was shown by the individual suffering from OCD in her youth. The amelioration in these two patients has been maintained for 2 and 6 years, respectively, whereas the course of HD is that of a progressive deterioration. CONCLUSIONS: Firm conclusions to explain these results cannot be drawn. However, a hypothetical involvement of the serotonergic system, suggested by the excess of OCD in the pedigree, seems supported by the response of these two individuals to fluoxetine. It may be worth further exploring the value of the psychiatric picture in selecting the appropriate treatment for at least some cases of HD.
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