The role of conditional drug responses in tolerance to the hypothermic effects of ethanol

The role of predrug cues in tolerance to ethanol-induced hypothermia was investigated in two experiments. The results of Experiment 1 demonstrated that tolerance was displayed only when the drug was administered in conjunction with environmental stimuli that had, in the past, accompanied ethanol administration. A conditional hyperthermic response was elicited when a placebo, instead of ethanol, was administered in conjunction with the usual ethanol cues. Results of Experiment 2 suggested that tolerance to ethanol-induced hypothermia can be extinguished by repeated placebo injections. These results indicate that associative processes, previously demonstrated to modulate opiate tolerance, also modulate ethanol tolerance.     

Inhibitory effects of MK-801 on contextual sensitization to climbing behavior and on development of tolerance to hypothermia induced by a single high dose of apomorphine

A single high dose of apomorphine (10 mg x kg(-1)) produced not only contextual sensitization to and conditioning of climbing behavior, but also context-independent tolerance to hypothermia. MK-801 (0.15 and 0.3 mg x kg(-1)) inhibited contextual sensitization to and conditioning of climbing behavior. Development of tolerance to hypothermia was also inhibited by MK-801. Dopamine D1 antagonist, SCH23390 (0.5 mg x kg(-1)), but not D2 antagonist, sulpiride, inhibited sensitization to and conditioning of climbing behavior. D2 antagonist, sulpiride (50 mg x kg(-1)), but not D1 antagonist, SCH23390, inhibited development of tolerance to hypothermia. These results suggest that MK-801 inhibited contextual sensitization to climbing behavior and development of tolerance to hypothermia through glutamatergic modulation of dopaminergic functions at dopamine receptors.     

Eyeblink conditioning anomalies in bipolar disorder suggest cerebellar dysfunction

Objectives:  Accumulating research implicates the cerebellum in non-motor psychological processes and psychiatric diseases, including bipolar disorder (BD). Despite recent evidence that cerebellar lesions have been documented to trigger bipolar-like symptoms, few studies have directly examined the functional integrity of the cerebellum in those afflicted with BD.
Methods:  Using a single-cue delay eyeblink conditioning procedure, the functional integrity of the cerebellum was examined in 28 individuals with BD (9 manic, 8 mixed, and 11 euthymic) and 28 age-matched healthy controls.
Results:  Analysis of the bipolar group as a whole indicated a conditioned response acquisition and timing deficit compared to controls. However, when the bipolar group was categorized according to mood state (mixed, manic, euthymic), individuals tested during mixed episodes were strikingly impaired, performing significantly worse than all other groups on both the acquisition and timing of conditioned responses.
Conclusions:  These findings extend prior research implicating cerebellar functional abnormalities in BD and suggest that cerebellar dysfunction may be associated with mood state and course of illness.     

The usefulness of operant conditioning procedures to assess long-lasting deficits following transient focal ischemia in mice

In this study, we examined a number of short and long-term sensorimotor, behavioural and cognitive consequences of an experimental ischemia induced by a 60-min right middle cerebral artery occlusion (MCAO) in 129S2 mice. During 14 days after surgery, a classical sensorimotor assessment was conducted using hanging wire test, negative geotaxis test, grip strength test, accelerated rotarod test and locomotor activity-meter. In order to provide a technique for the assessment of more resistant consequences of ischemia on fine psychomotor control, the peak procedure (a modified version of the operant fixed-interval schedule of reinforcement) was used. This procedure also helped to objectify temporal perception in mice five weeks following surgery. On several sensorimotor tests, ischemic mice showed some degree of impairment which rapidly tended to improve after stroke, a profile of results substantially consistent with previous studies. Five weeks post-surgery, ischemic mice tested with the peak procedure exhibited a moderate but yet significant temporal regulation impairment along with a reduced response rate compared to control mice. The present results suggest that the peak procedure and other derived operant schedules of reinforcement may provide useful and sensitive tools for the long-term assessment of both behavioural and cognitive aspects of the consequences of an experimental ischemia.     

Pavlovian conditioning of opioid and nonopioid pain inhibitory mechanisms in humans.

Learning processes such as respondent or Pavlovian conditioning are believed to play an important role in the development of chronic pain, however, their influence on the inhibition of pain has so far not been assessed in humans. The purpose of this study was the demonstration of Pavlovian conditioning of stress-induced analgesia in humans and the determination of its opioid mediation. In a differential classical conditioning paradigm two different auditory stimuli served as conditioned stimuli and mental arithmetic plus white noise as unconditioned stimulus. Subsequent to four conditioning trials naloxone or placebo was applied in a double-blind fashion on two test days. Both pain threshold and pain tolerance showed conditioned stress-induced analgesia. Pain tolerance was affected by naloxone whereas pain threshold was not. The data of this study show that stress analgesia can be conditioned in humans and that it is at least partially mediated by the endogenous opioid system. Learning processes also influence pain inhibitory processes in humans and this effect might play a role in the development of chronic pain.     

Latent inhibition of conditioned taste aversion in rats with excitotoxic dorsal hippocampal lesions

The hippocampus plays crucial roles for the acquisition of latent inhibition in different associative learning procedures, such as fear conditioning. However, the involvement of the hippocampus in the latent inhibition of conditioned taste aversion (CTA) is uncertain. Because different subregions of the hippocampus are associated with distinct functions, it is possible that specific regions of this structure are selectively involved in this learning. To explore the relationship between the dorsal hippocampal region and the latent inhibition of CTA, we analyzed the behavioral effects of excitotoxic lesions of the dorsal hippocampus vs. sham lesions in this paradigm. The results provide no evidence that the latent inhibition of CTA is compromised in rats with excitotoxic dorsal hippocampal lesions. The differential involvement of specific hippocampal regions in the latent inhibition of other associative learning paradigms is briefly discussed. © 2015 Wiley Periodicals, Inc.     

The effect of heterotopic noxious conditioning stimulation on Aδ‐, C‐ and Aβ‐fibre brain responses in humans

Human studies have shown that heterotopic nociceptive conditioning stimulation (HNCS) applied to a given body location reduces the percept and brain responses elicited by noxious test stimuli delivered at a remote body location. It remains unclear to what extent this effect of HNCS relies on the spinal–bulbar–spinal loop mediating the effect of diffuse noxious inhibitory controls (DNICs) described in animals, and/or on top‐down cortical mechanisms modulating nociception. Importantly, some studies have examined the effects of HNCS on the brain responses to nociceptive input conveyed by Aδ‐fibres. In contrast, no studies have explored the effects of HNCS on the responses to selective nociceptive C‐fibre input and non‐nociceptive Aβ‐fibre input. In this study, we measured the intensity of perception and event‐related potentials (ERPs) to stimuli activating Aδ‐, C‐ and Aβ‐fibres, before, during and after HNCS, obtained by immersing one foot in painful cold water. We observed that (i) the perceived intensity of nociceptive Aδ‐ and C‐stimuli was reduced during HNCS, and (ii) the ERPs elicited by Aδ‐ and Aβ‐ and C‐stimuli were also reduced during HNCS. Importantly, because Aβ‐ERPs are related to primary afferents that ascend directly through the dorsal columns without being relayed at spinal level, the modulation of these responses may not be explained by an influence of descending projections modulating the transmission of nociceptive input at spinal level. Therefore, our results indicate that, in humans, HNCS should be used with caution as a direct measure of DNIC‐related mechanisms.