Behavioural brain research
-
The aim of this experiment was to investigate the effects of nicotinic acetylcholine receptor (nAChR) agonism and antagonism on learning. Eyeblink classical conditioning (750ms delay procedure) was tested for 15 daily sessions in a total of 82 young rabbits: 58 rabbits were tested in the paired procedure when the conditioned stimulus (CS) was always followed by the unconditioned stimulus (US), and 24 rabbits were tested in the explicitly unpaired procedure in which CS and US presentations were independent. We used the nAChR agonists nicotine and GTS-21 (a selective alpha7 nAChR partial agonist that antagonizes alpha4beta2 nAChRs) and the relatively nonselective nAChR antagonist, mecamylamine. ⋯ Both GTS-21 and nicotine reversed the deleterious effect of mecamylamine on the acquisition of conditioned responses. Combinations of GTS-21 or nicotine and mecamylamine did not cause sensitization or habituation in the unpaired condition. Reversal of mecamylamine-induced learning deficits by nicotine and GTS-21 suggests that nAChR agonists may have efficacy in ameliorating deficits caused by the loss of some types of nAChRs in diseases such as AD.
-
The ability to voluntarily transit from one whole-body movement to another is based on the multisensory integration of visual, vestibular, and somatosensory information. The role of functional sensory ranges and mechanical constraints on the ability to voluntarily transit between whole-body movements was studied by requiring subjects to switch from a head-fixed-to-surface to head-fixed-in-space postural pattern (and vice versa). The head-fixed-to-surface pattern required an erect stance characterized by an in-phase relationship between center of pressure (CoP) and platform motion. ⋯ These findings demonstrate separate control processes for upper- and lower-body motion and that functional sensory ranges and mechanical constraints can facilitate or inhibit voluntary production of whole-body movements based on these control processes. The results are discussed in reference to neurological substrates that may be involved in the planning and execution of motor set-switching. The experimental protocol we employ may also have application as a diagnostic tool for the evaluation of postural deficits.
-
Comparative Study
Facilitatory effect of the dopamine D4 receptor agonist PD168,077 on memory consolidation of an inhibitory avoidance learned response in C57BL/6J mice.
The still unknown contribution of the D4 receptors to memory consolidation was studied examining the memory effects of the dopamine D4 agonist PD168,077, the putative dopamine D4 antagonist L745,870, their mutual combination, and the combination of the D4 agonist with representative compounds acting as agonist or antagonist on the D1, D2 and the D3 receptors. Memory consolidation was assessed in C57BL/6J mice using the one-trial step-through inhibitory avoidance task, the compounds being injected immediately after training (foot-shock) and performance measured 24h later. PD168,077 (0.5-10mg/kg) dose-dependently improved memory performance and L745,870 (0.05-5mg/kg) at doses lower than 1mg/kg increased and at doses higher than 1mg/kg impaired memory performance. ⋯ The dopamine D3 antagonist U99194A (2.5-10mg/kg) did not affect the promnesic effects induced by the D4 agonist, which nevertheless abolished the U99194A-induced promnesic effects. Additionally, the amnesic effects produced by the D3 agonist 7-OH-DPAT (0.01-1 microg/kg) was attenuated by PD168,077. These results suggest a potential role of dopamine D4 receptors in memory consolidation, which would be similar to that of the D1 and D2 receptors and probably opposite to that of the D3 receptors.
-
Animals made ill by intraperitoneal injection with toxins, such as lithium chloride (LiCl) or lipopolysaccharides (LPS), or presented with cues associated with LiCl become hyperalgesic [Pain 56 (1994) 227]. The descending pronociceptive neurocircuitry and spinal pharmacology that underlie these effects bear the same features as those that mediate analgesic tolerance to morphine [Neurosci. Biobehav. ⋯ Furthermore, these effects occurred in the absence of detectable hyperalgesia indicating that illness-induced tolerance was not the result of an increase in pain sensitivity offsetting analgesia. Finally, rats tested in a context associated with LiCl demonstrated less morphine analgesia than rats tested in a context not associated with LiCl or rats naive to LiCl suggesting that illness activates descending mechanisms that antagonize analgesia rather than simply desensitizing opioid receptors. Thus, in addition to provoking hyperalgesia, illness-inducing agents also activate endogenous antianalgesic mechanisms.
-
Dopamine (DA) neurons of the substantia nigra (SN) and ventral tegmental area (VTA) respond to a wide category of salient stimuli. Activation of SN and VTA DA neurons, and consequent release of nigrostriatal and mesolimbic DA, modulates the processing of concurrent glutamate inputs to dorsal and ventral striatal target regions. According to the view described here, this occurs under conditions of unexpected environmental change regardless of whether that change is rewarding or aversive. ⋯ A DA signal of salient unexpected event occurrence, from this framework, gates the throughput of the orbitofrontal glutamate reward input to the striatum just as it gates the throughput of corticostriatal sensory and motor signals needed for normal response execution. Processing of these incoming signals is enhanced when synaptic DA levels are high, because DA enhances the synaptic efficacy of strong concurrent glutamate inputs while reducing the efficacy of weak glutamate inputs. The impairments in motor performance and incentive motivational processes that follow from nigrostriatal and mesolimbic DA loss can be understood in terms of a single mechanism: abnormal processing of sensorimotor and incentive motivation-related glutamate input signals to the striatum.