Pharmacology, biochemistry, and behavior
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Pharmacol. Biochem. Behav. · May 1998
Olfactory cues and morphine-induced conditioned analgesia in rats.
In a Pavlovian conditioning procedure, rats were exposed to an odor conditioned stimulus (CS) and then were given morphine with its effect serving as the unconditioned stimulus (US). After four CS-US pairings, the CS was tested alone to assess the presence of an analgesic conditioned response (CR) using a hot-plate test. In Experiment 1a, two groups were conditioned by pairing either 10 mg/kg morphine or saline with an odor CS. ⋯ Experiment 2 characterized the dose-effect curve (0, 3, 10, and 30 mg/kg morphine) using an odor conditioning procedure. The dose-effect curve showed an inverted U-shaped function, with the 10 mg/kg morphine group having significantly longer paw-lick latencies compared to all other groups. This finding contrasts with the monotonically ascending dose-effect curve for the analgesic unconditioned response (UR) to morphine.
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Pharmacol. Biochem. Behav. · May 1998
Antagonism of ketamine-induced anesthesia by an inhibitor of nitric oxide synthesis: a pharmacokinetic explanation.
Because ketamine is an antagonist of NMDA receptors, and because some NMDA receptors activate nitric oxide synthesis in brain, this study examined if nitric oxide synthase (NOS) inhibition by L-NAME altered the course of ketamine-induced behavioral impairment. Rats given progressive doses of L-NAME until NOS activity was inhibited at least 90% displayed reduced depth and duration of behavioral depression after i.m. ketamine. ⋯ The content of norketamine and its adventitial extraction product were similarly reduced relative to control but the ratio of metabolites to ketamine was not significantly altered (p > 0.05) in brain. The decreased delivery of ketamine into brain, perhaps due to L-NAME-induced alterations in blood flow, may explain the reduced behavioral response to ketamine in these rats.
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Pharmacol. Biochem. Behav. · Mar 1998
Comparative StudyDifferential involvement of opioid receptors in intrathecal butorphanol-induced analgesia: compared to morphine.
The present experiments were performed to investigate the differential involvement of the opioid receptor subtypes in the antinociception of intrathecal (IT) butorphanol compared to IT morphine. A single dose (26 nmol) of IT nor-binaltorphimine (nor-BNI), beta-funaltrexamine (beta-FNA), and naltrindole (NTI) demonstrated a significant attenuation in the overall antinociception of IT butorphanol (52 nmol) or IT morphine (26 nmol). However, IT butorphanol elicits thermal antinociceptive effect through kappa > delta > or = mu, whereas morphine acts on mu >delta > kappa. These results indicate that the antinociceptive effect of both IT butorphanol and IT morphine are mediated through mu, delta, and kappa opioid receptors in different relative orders.
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Pharmacol. Biochem. Behav. · Mar 1998
Effects of chlordiazepoxide on opioid-induced antinociception and respiratory depression in restrained rats.
This study investigates the influence of possible stress due to housing in Bolman cages on antinociception and on respiratory depression following opioid administration. To evaluate the functional role of this stressor and to modulate it, rats were subcutaneously pretreated with the anxiolytic chlordiazepoxide (CDP; 10 mg/kg) or saline (SAL) before the immobilization in the Bolman cages and before the intravenous administration of small doses of morphine (MOR), sufentanil (SUF), or vehicle (VEH). Antinociception, respiratory impairment and stress were evaluated by means of the tail-flick latency, blood gas analysis, and serum corticosterone (CS), adrenocorticotropic hormone (ACTH), and prolactin (PRL) determinations. ⋯ Also, MOR without CDP prevented the increases in CS, but the opioid intrinsically increased ACTH. These results indicate that restraint in Bolman cages in the present setup, with animals recovering for several hours in these cages after being equipped with an arterial catheter, is stressful but without any significant effect on the opioid-induced antinociception. Pretreatment with an anxiolytic benzodiazepine only minimally affected the outcome of the opioids on respiratory depression and pointed to a stress-reducing effect of low doses of the opioids, especially sufentanil.
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Pharmacol. Biochem. Behav. · Dec 1997
Effects of microinjections of cholecystokinin and neurotensin into lateral hypothalamus and ventral mesencephalon on intracranial self-stimulation.
Changes in intracranial self-stimulation (ICSS) evoked from ventral tegmental area-substantia nigra (VTA-SN) and lateral hypothalamus-medial forebrain bundle (LH-MFB) before and after microinjections of sulfated cholecystokinin octapeptide (CCK-8S) and unsulfated cholecystokinin (CCK-8US), neurotensin tridecapeptide ([D-Tyr11]NT(1-13) or [DTrp11]NT(1-13)) into either VTA-SN or LH-MFB were assessed. The current intensity was fixed at a level to obtain 60-70% of the maximal asymptotic rate. CCK-8S (0.10 microg/0.5 microl and 0.25 microg/0.5 microl) into VTA-SN resulted in dose-dependent decreases in VTA-SN ICSS of 38-42% and 78-92%, respectively, without affecting the ICSS of LH-MFB. ⋯ Similar injections of these peptides into LH-MFB did not change the responding rates for LH-MFB ICSS or VTA-SN ICSS. Increasing the current intensity reversed the inhibitory effect of CCK-8S and [D-Trp11]NT(1-13) on VTA-SN ICSS and restored basal preinjection rates of responding. These results suggest that CCK(A) and NT1 receptor mechanisms in the ventral tegmentum in association with dopamine neurotransmission may be important in mediating the rewarding effects of VTA-SN ICSS but not LH-MFB ICSS.