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  • 1
    Electronic Resource
    Electronic Resource
    Aversive effects of the C-fragment of Substance P in the dorsal periaqueductal gray matter (1998)
    Springer
    Experimental brain research 123 (1998), S. 84-89 
    Details
    ISSN: 1432-1106
    Keywords: Key words Substance P ; Dorsal periaqueductal gray ; Behavioral activation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  There has been an increasing interest in the role of neuropeptides in the integration of brain functions. Besides the well-known positive-reinforcing effects of Substance P (SP) in prosencephalic regions, a role of this neuropeptide in the generation of aversive states in mesencephalic structures has also been envisaged. Evidence from a previous study suggests an involvement of SP in the neural substrates of aversion in the dorsal periaqueductal gray matter (DPAG). In the present study, we investigate whether N- and C-terminal fragments of Substance P are responsible for the effects produced by microinjections of SP into the dorsal periaqueductal gray. The results show that SP and its C-terminal fragment SP7–11 produced a behavioral activation with increases in locomotor activity, grooming, and rearings, while the N-terminal fragment SP1–7 produced only an increase in vertical exploratory activity. The effects were more pronounced with intermediate doses of SP and its C-fragment, confirming the characteristic bell-shaped dose-effect function of this neuropeptide. The proaversive effects observed with DPAG microinjections of these neuropeptides in the present study gain further relevance when combined with previous reports showing unconditioned and conditioned aversive effects following DPAG microinjections of SP in the place aversion and the elevated plus maze tests, two widely used animal models of anxiety. These results confirm previous data showing that SP has a modulatory role in the DPAG and that its effects are probably due to its C-terminal fragment.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002210050547
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  • 2
    Electronic Resource
    Electronic Resource
    A comparative study of the effects of morphine in the dorsal periaqueductal gray and nucleus accumbens of rats submitted to the elevated plus-maze test (1999)
    Springer
    Experimental brain research 129 (1999), S. 260-268 
    Details
    ISSN: 1432-1106
    Keywords: Key words Opioids ; µ-Receptors ; κ-Receptors ; Aversion ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  We studied the effects of morphine injected either systemically or into the dorsal periaqueductal gray (DPAG) or nucleus accumbens (NA) using conventional and ethological analyses of behavior of rats submitted to the elevated plus-maze test with transparent walls. Intraperitoneal morphine (0.1 mg/kg and 0.3 mg/kg) increased both standard and ethological measures, expressing general exploratory activity such as total arm entries, end-exploration, scanning, head-dipping, and rearing. Morphine 10 (7.6 µg/µl) and 30 nmol (23 µg/µl) injected into nucleus accumbens produced similar effects, which were blocked by i.p. naltrexone (2.0 mg/kg), an opioid antagonist with good affinity for µ-opioid receptors. Morphine injected into the DPAG produced either antiaversive (10 nmol) or aversive effects (30 nmol), which respectively reduced and increased entries and time spent in the open arms and behaviors associated with risk assessment (peeping out, stretched attend postures, and flat back approach). The proaversive effects were inhibited by i.p. norbinaltorphimine (2.0 mg/kg), a selective inhibitor for κ-opioid receptors. These findings support the contention that at least some of the motivational effects of morphine may be due to activation of opioid mechanisms in nucleus accumbens, and DPAG has neural substrates for antiaversive and aversive effects of morphine. Moreover, on the basis of previous and present data obtained in this laboratory, it is suggested that stimulation of µ-opioid receptors inhibits and stimulation of κ-receptors activates the neural substrate of aversion in the DPAG. On the other hand, the increase in exploratory behavior due to interaction of morphine with µ-opioid receptors in the nucleus accumbens may be due to the stimulation of the interface between neural substrates of motivation and motor output in this structure.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002210050896
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  • 3
    Electronic Resource
    Electronic Resource
    Effects of blockade of 5-HT2 receptors and activation of 5-HT1A receptors on the exploratory activity of rats in the elevated plus-maze (1992)
    Springer
    Psychopharmacology 107 (1992), S. 135-139 
    Details
    ISSN: 1432-2072
    Keywords: 5-HT1A receptors ; 5-HT2 receptors ; Anxiety ; Gepirone ; Ketanserin ; Plus-maze test
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Acute administration of gepirone, a 5-HT1A agonist, caused a dose dependent (1–10 mg/kg, IP) reduction in the locomotor activity (open and closed arms) of rats tested in the elevated plus-maze. However, rats housed in individual cages and submitted to chronic treatment with gepirone (10 mg/kg PO) showed a marked increase in the percentages of number and time spent in the open arms as compared to controls. These results are compatible with the idea that the antiaversive effect due to long-term treatment with 5-HT1A agonists is the result of a progressive desensitization of the somatodendritic 5-HT autoreceptor with the consequent recovery of firing rate of 5-HT neurons along with an activation of normosensitive postsynaptic 5-HT neurons. Ketanserin caused a biphasic effects on the exploratory behavior of rats in the plus-maze. The lower dose (0.5 mg/kg) decreased the aversion to the open arms and the higher dose (1.0 mg/kg) caused an unspecific decrease in the overall activity of the animals. Ketanserin is supposed to have antagonistic action on 5-HT2 and on α-adrenergic receptors. As prazosin (0.5–1.0 mg/kg), an α-adrenergic receptor blocker, did not present any significant effect in the present work it is suggested that the effects of the lower dose of ketanserin was due to its high antagonistic action on 5-HT2 receptors.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF02244978
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  • 4
    Electronic Resource
    Electronic Resource
    Effects of microinjections of μ and κ receptor agonists into the dorsal periaqueductal gray of rats submitted to the plus maze test (1995)
    Springer
    Psychopharmacology 120 (1995), S. 470-474 
    Details
    ISSN: 1432-2072
    Keywords: DPAG ; Opioids ; μ Receptors ; κ Receptors ; Escape ; Aversion ; Elevated plus maze
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Several lines of evidence have shown that aversive states are under the influence of opioid mechanisms in the dorsal periaqueductal gray (DPAG). In order to characterize the type of opioid receptors involved in these effects in this work we injected DAMGO and U50,488H,μ andκ selective agonists, respectively, directly in this structure. Rats implanted with chemitrode in the DPAG were submitted to the elevated plus maze test for 5 min. The effects of DAMGO (0.1–1 nmol/0.2μl) and U50,488H (1–10 nmol/0.2 µl) following administration into DPAG were studied. Low doses of DAMGO (0.1 and 0.3 nmol) caused dose-dependent increases in the number of entries and time spent in the open arms while an overall deficit in the exploratory activity was produced by the higher dose used (1.0 nmol). Clear aversive effects were observed following the administration of U50,488H in the DPAG. The antiaversive effects of 0.3 nmol DAMGO were inhibited by the intraperitoneal administration of theμ receptor antagonist naltrexone (2.0 mg/kg, IP) whereas the aversive effects of 5.0 nmol U50,488H were antagonized by the selectiveκ receptor antagonist nor-binaltorphimine (1.0 mg/kg, IP). It is suggested that activation ofμ receptors inhibit and κ receptors enhance the neural substrate of aversion in the DPAG.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF02245820
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  • 5
    Electronic Resource
    Electronic Resource
    Defensive reactions are counteracted by midazolam and muscimol and elicited by activation of glutamate receptors in the inferior colliculus of rats (1999)
    Springer
    Psychopharmacology 142 (1999), S. 360-368 
    Details
    ISSN: 1432-2072
    Keywords: Key words Inferior colliculus ; Aversion ; Glutamate ; Muscimol ; Midazolam
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  The inferior colliculus is involved in conveying auditory information of an aversive nature to higher cortical structures. Gradual increases in the electrical stimulation of this structure produce progressive aversive responses from vigilance, through freezing, until escape. Recently, we have shown that microinjections of NMDA into the inferior colliculus mimic these aversive effects and that the neural substrates responsible for learned escape behavior in the inferior colliculus are regulated by GABA−benzodiazepine mechanisms. In the present study, we extend these observations showing that unlearned aversive responses are also depressed by muscimol and midazolam, both GABA-benzodiazepine agonists, and that microinjection of glutamate, an excitatory amino acid, into the inferior colliculus can trigger freezing responses. Electrical stimulation of the inferior colliculus of rats placed inside an open field allowed the determination of thresholds for the aversive responses, alertness, freezing and escape. Systemic administration (3 and 5.6 mg/kg) as well as microinjections into the inferior colliculus of the anxiolytic compound midazolam (10, 20 and 40 nmol) caused increases in threshold for these aversive responses. Similar results were obtained following microinjections of the GABA-A agonist muscimol (0.1, 1 and 5 nmol) into this brainstem structure. Microinjections of low doses of glutamate (5 nmol), presumed to activate mainly AMPA/kainate receptors, into the ventrolateral division of the central nucleus of the inferior colliculus of rats placed inside a circular arena induced aversive reactions, characterized by freezing responses. However, higher doses of glutamate caused no apparent effects. GDEE, an AMPA/kainate receptor antagonist, inhibited, whereas AP7, a NMDA receptor antagonist, did not influence these responses. It is suggested that GABA-benzodiazepine processes modulate the expression of defensive reactions in the inferior colliculus and that activation of fast-acting excitatory amino acid receptors in this midbrain region can trigger the initial steps of the defense reaction without eliciting the motor explosive behavior usually seen following the activation of NMDA receptors.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002130050900
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    Paper (German National Licenses)
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