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E T Iwamoto

Publications and source records attributed to E T Iwamoto.

At least 19 recordsLinked to original sources
PubMed1994

Pharmacological evidence that nitric oxide mediates the antinociception produced by muscarinic agonists in the rostral ventral medulla of rats.

The present study was designed to characterize the antinociception produced by the administration of a muscarinic agonist, (+)-cis-methyldioxolane, into the rostral ventral medulla (RVM) of male Sprague-Dawley rats. Seven days after the implantation of 25-gauge stainless-steel guide cannulae, animals were injected with graded doses of (+)-cis-methyldioxolane, and antinociception was assessed by using the 52 degrees C hot-plate and tail-flick tests in a single-blind design. (+)-cis-Methyldioxolane produced dose-related hot-plate and tail-flick antinociception for 30 to 45 min peaking 5 to 10 min after RVM injection. The ED50 values of (+)-cis-methyldioxolane in the hot-plate and tail-flick tests were 2.4 and 1.7 nmol, respectively. Five-minute preinjections with 0.35 nmol of the muscarinic M1 receptor blocker pirenzepine competitively antagonized the antinociception produced by (+)-cis-methyldioxolane. The antinociception produced by RVM injections of the muscarinic M2 receptor blocker methoctramine was additive to the antinociceptive effects of (+)-cis-methyldioxolane when the two antinociceptive effects of (+)-cis-methyldioxolane when the two agents were combined. Twenty four-hour pretreatment of the RVM with the irreversible muscarinic receptor antagonist 4-diphenylacetoxy-N-[2-chloroethyl]-piperidine mustard blocked the antinociceptive effects of (+)-cis-methyldioxolane completely. Administration of 6 nmol of the nitric oxide synthase inhibitor L-NG-nitroarginine into the RVM competitively antagonized the antinociception produced by (+)-cis-methyldioxolane and (+)-muscarine in the hot-plate and tail-flick tests. Pretreatment with 100 nmol of L-arginine, but not D-arginine, significantly reversed the inhibitory effects of L-NG-nitroarginine on (+)-cis-methyldioxolane-produced antinociception. Pretreatment with 100 nmol of the guanylyl cyclase inhibitor methylene blue into the RVM profoundly antagonized the antinociception produced by (+)-cis-methyldioxolane. Neither buffer L-NG-nitroarginine, L-arginine-D-arginine or methylene blue altered hot-plate or tail-flick nociception when injected alone into the RVM. In contrast, either dibutyryl cyclic GMP or 8-bromo cyclic GMP, membrane-permeable cyclic GMP analogs, produced hot-plate and tail-flick antinociception when injected alone into the RVM. These data are consistent with the hypothesis that the antinociception produced by muscarinic stimulation of the RVM is mediated by an L-arginine/nitric oxide/cyclic GMP cascade.

Amino Acid Oxidoreductases↗
PubMed1994

Pharmacologic evidence that spinal muscarinic analgesia is mediated by an L-arginine/nitric oxide/cyclic GMP cascade in rats.

This study was designed to determine if the antinociception produced by intrathecally (i.t.) administered muscarinic agonists in male Sprague-Dawley rats is mediated by an L-arginine/nitric oxide/cyclic GMP cascade. Seven days after implantation of intrathecal catheters, antinociception was produced with graded doses of (+)-cis-methyldioxolane (CD). The ED50 values for CD in the hot-plate and tail-flick tests were 2.6 and 2.0 nmol, respectively. The corneal and righting reflexes, as well as stepping and negative geotaxic responses, were not affected by CD. Six-minute pretreatment with 50 nmol of the nitric oxide synthase inhibitor L-NG-nitroarginine (NNR) significantly inhibited CD-produced hot-plate and tail-flick antinociception as evidenced by 6-fold shifts to the right of the CD dose-response curves. Coadministration of 150 nmol of L-arginine with NNR reversed the NNR-induced inhibition of the antinociception produced by CD. D-Arginine was without effect. Pretreatment with 500 nmol of the guanylyl cyclase inhibitor methylene blue also antagonized the antinociception produced by CD in both the hot-plate and tail-flick tests. In parallel with CD, coadministration of L-arginine with NMR reversed the NMR-induced inhibition of (+)-muscarine-produced antinociception in both nociceptive tests. Intrathecal administration of buffer, 50 nmol of NNR, 150 nmol of L- or D-arginine or 500 nmol of methylene blue, did not alter nociceptive responses when injected alone. In contrast, i.t. administration of the membrane-permeable cyclic GMP analogs, dibutyryl cyclic GMP and 8-bromo cyclic GMP, produced antinociception in both nociceptive tests when injected alone.(ABSTRACT TRUNCATED AT 250 WORDS)

Analgesia↗
PubMed1993

Multiple spinal mediators in parenteral nicotine-induced antinociception.

The role of spinal mechanisms in subcutaneous (s.c.) nicotine-induced antinociception was examined in male Sprague-Dawley rats using the hot-plate and tail-flick tests. Nicotine (0.125, 0.25, 0.375 or 0.5 mg/kg s.c.) produced a dose-related inhibition of nociception in both tests. Although increasing negative geotaxis response times slightly, no significant alteration of other motor reflexes was observed with 0.375 mg/kg of s.c. nicotine. Microinjection of 7 nmol of the high-affinity choline uptake inhibitor hemicholinium-3 into the rostral ventral medulla completely inhibited the antinociception produced by 0.375 mg/kg of s.c. nicotine. Intrathecal (i.t.) injection of 61 nmol of nicotine (in 10 microliter buffer) produced no changes in hot-plate or tail-flick test response latencies. Nicotine-induced antinociception was blocked by a variety of i.t. antagonists injected 12 min before s.c. injection of 0.375 mg/kg of nicotine. In both tests, i.t. pretreatment with 0.1 mumol (in 10 microliter buffer) of scopolamine, methysergide, yohimbine, idazoxan, mecamylamine or 0.2 mumol of atropine attenuated nicotine-induced increases in test response latencies. Pretreatment with 0.1 mumol of atropine attenuated nicotine-induced increases in tail-flick test, but not in the hot-plate test. Pretreatment with 0.1 mumol of i.t. prazosin or naloxone produced no changes in nicotine-induced increases in test response latencies in either test. These data suggest that the antinociception produced by s.c. nicotine is mediated via a number of sites in the spinal cord, including alpha-2 adrenergic, serotonergic and muscarinic cholinergic.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenergic alpha-Antagonists↗
PubMed1993

Characterization of the antinociception produced by intrathecally administered muscarinic agonists in rats.

The present study was designed to characterize the antinociception produced by the administration of a potent muscarinic agonist into the intrathecal space of the lumbar spinal cord of male Sprague-Dawley rats. Seven days after surgical implantation of intrathecal catheters, animals were injected with graded doses of (+)-cis-methyldioxolane. (+)-cis-Methyldioxolane produced hot-plate and tail-flick antinociception for up to 90 min, peaking 5 to 30 min after injection. The dose of (+)-cis-methyldioxolane that inhibited nociception by 50% was 12 nmol in both the hot-plate and tail-flick tests. This antinociception was not accompanied by a general depression of other spontaneous motor responses. The tissue concentration of (+)-cis-methyl-dioxolane in the lumbar spinal cord present at the time of maximal hot-plate and tail-flick antinociception was approximately 12 microM. In similarity to (+)-cis-methyldioxolane, intrathecally administered (+)-muscarine also produced strong hot-plate and tail-flick antinociceptive responses. In contrast, intrathecally administered N-methylcarbachol, a nicotinic agonist, had no effect on nociception. Five-minute pretreatment with graded doses of pirenzepine, methoctramine, idazoxan, LY53857, or S-(-)-zacopride each significantly antagonized hot-plate and tail-flick antinociception produced by 37.5 nmol of (+)-cis-methyldioxolane in a dose-related manner with median effective antagonist doses in the range of 0.4 to 2.2 nmol. Intrathecal pretreatment with graded doses of prazosin or naloxone enhanced the antinociception produced by (+)-cis-methyldioxolane in the tail-flick but not the hot-plate tests. Intrathecal vehicle, S(-)-propranolol or mecamylamine did not alter (+)-cis-methyldioxolane-induced antinociception. The data suggest that the antinociceptive responses produced by intrathecally administered (+)-cis-methyldioxolane involve the stimulation of muscarinic M1 and/or M2 cholinergic receptors, and may also involve activation of alpha-2 adrenergic, 5-hydroxytryptamine1c/2 and 5-hydroxytryptamine3 serotonergic receptor systems at the level of the lumbar cord.

Adrenergic alpha-Antagonists↗
PubMed1993

Adrenergic, serotonergic and cholinergic components of nicotinic antinociception in rats.

The present study was designed to determine the degree of participation of opioid, noradrenergic, serotonergic and cholinergic systems of the lumbar spinal cord in the antinociception produced by nicotinic stimulation of the pedunculopontine tegmental nucleus (PPTg) or nucleus raphe magnus (RMg). Adult, male Sprague-Dawley rats were implanted subcortically with 25-gauge cannulas into the PPTg or RMg. The animals were also implanted with intrathecal catheters terminating in the subarachnoid space just rostral to the lumbar enlargement. Seven days after surgery, animals were injected with 15 to 100 nmol of various receptor antagonists intrathecally 10 min before microinjections of 40 nmol of N-methylcarbachol (NMC) into the PPTg or RMg. Doses of antagonists were chosen which did not induce motor disturbances and did not alter hot-plate or tail-flick nociception when administered alone. NMC produced hot-plate and tail-flick antinociception for 20 to 25 min, peaking 5 to 10 min after either PPTg or RMg microinjection. Intrathecal administration of 50 nmol of idazoxan, 100 nmol of S-(-)-propranolol, 20 nmol of LY53857, 25 nmol of S-(-)-zacopride, 100 nmol of pirenzepine or 50 nmol of methoctramine each antagonized in part the antinociception produced by PPTg or RMg microinjections of 40 nmol of NMC. Intrathecal administration of 100 nmol of naloxone or 100 nmol of prazosin enhanced the antinociceptive effects of NMC. Intrathecal vehicle or 100 nmol of mecamylamine did not alter NMC-induced antinociception. Complete antagonism of PPTg-administered NMC antinociception was achieved only when animals were pretreated intrathecally with combinations of at least three of the following four antagonists, 20 nmol of S-(-)-zacopride, 15 nmol of LY53857, 25 nmol of idazoxan and 50 nmol of methoctramine. The data suggest that the antinociceptive responses produced by nicotinic stimulation of the PPTg or RMg have similar pharmacologic profiles, and are redundantly mediated via alpha-2 adrenergic, 5-HT1c/2 and 5-HT3 serotonergic, and M2 cholinergic receptor interactions in the lumbar spinal cord.

Adrenergic Antagonists↗
PubMed1991

Characterization of the antinociception induced by nicotine in the pedunculopontine tegmental nucleus and the nucleus raphe magnus.

The antinociceptive effect of subcortically administered nicotine was investigated in the rat using the hot-plate and tail-flick tests. Adult male Sprague-Dawley rats were implanted with guide cannulas aimed at 185 sites in the forebrain, midbrain and hindbrain. After 1 week, nicotine was injected in 0.5 microliter of 50 mM phosphate buffer, pH 7.4. The pedunculopontine tegmental nucleus (PPTg) of the mesopontine tegmentum and the nucleus raphe magnus (NRM) of the ventral medulla were the most sensitive sites of nicotine-induced antinociception. The median effective doses of nicotine to inhibit hot-plate or tail-flick nociception after PPTg or NRM administration ranged between 1.4 and 3 nmol. The lack of effect of s.c. injections of naloxone on the antinociception induced by nicotine in the PPTg or NRM ruled out endogenous opioid mechanisms. Coadministration of mecamylamine or pirenzepine with nicotine into the NRM competitively antagonized nicotine-induced antinociception. The administration of the muscurinic cholinergic type 2 receptor antagonist methoctramine into the NRM produced a strong antinociceptive response which was blocked by prior treatment of the NRM with hemicholinium-3. Hemicholinium-3 pretreatment of either the PPTg or the NRM antagonized the antinociception induced by nicotine at these sites. Hemicholinium-3 pretreatment of the NRM also antagonized the antinociception produced by s.c. administered nicotine. The antinociceptive effects of nicotine injected in the PPTg were blocked by procainamide injections in the NRM; however, the antinociceptive effects of nicotine injected in the NRM were not blocked by bilateral injections of procainamide in the PPTg. Both lesioning the PPTg with ibotenic acid and pretreating the NRM with hemicholinium-3 abolished completely the antinociception induced by nicotine or (+)-cis-dioxolane microinjections into the PPTg. However, neither ibotenic acid-induced nor electrolytic lesions of the PPTg alone altered CRL. The data support the existence of a tonically active cholinergic pathway which is under autoinhibitory control that originates in the PPTg, terminates in the NRM and modulates nociception by activating descending pain inhibitory systems relaying within the NRM.

Analgesia↗
PubMed1990

Nicotine conditions place preferences after intracerebral administration in rats.

A single-trial place conditioning procedure, one treatment and one non-treatment during two daily conditioning sessions followed by a single test session on the 3rd day, was used to examine the place conditioning effects of intracerebrally administered nicotine. In the first series of experiments, Sprague-Dawley male rats were implanted unilaterally with guide cannulas aimed at the lateral ventricle. After 1 week, rats received either "treatment" (nicotine in 2 microliters phosphate buffer or 2 microliters of buffer alone) or "no treatment" (no injections) before being placed in the black or white compartment of a three-compartment place-conditioning apparatus for 20 min. The next day the rats received the opposite treatment before being conditioned in the opposite compartment. On day 3, animals had free access to the entire apparatus for 15 min and the time spent in each compartment was recorded automatically. Even though the rats exhibited a baseline bias for the black compartment, intracerebroventricular nicotine induced positive place preferences relative to buffer control, i.e. if treatments were paired with the black compartment, nicotine enhanced the preference for the black compartment, and if the treatments were paired with the white compartment, nicotine induced a preference for the white compartment. In addition, the nicotine-induced preference response was antagonized by the co-intraventricular administration of mecamylamine. In a second series of experiments, animals were implanted unilaterally with guide cannulas aimed at the pendunculopontine tegmental nucleus of the mesopontine tegmentum. Nicotine microinjection, 1.2-18.5 nmol in 0.5 microliter buffer, induced a dose-dependent positive place preference response.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1990

Conditioned aversion after delay place conditioning with amphetamine.

Male, Sprague-Dawley rats received subcutaneous injections of either dextroamphetamine sulfate (AMP; 3.0 mg/kg) or vehicle [VEH (phosphate buffer); 1 ml/kg] immediately before (standard conditioning) or after (delay conditioning) conditioning sessions in a place-conditioning paradigm. AMP was paired for 4 conditioning sessions with one compartment of a three-compartment place-conditioning apparatus; VEH was paired for 4 conditioning sessions with another compartment. Animals were then tested for place preference or aversion by determining the proportion of time spent in each compartment during a 15-minute test session. Standard conditioning with AMP produced a place preference while delay conditioning produced a place aversion. Similar findings had earlier been reported from studies involving conditioned place-preferences and aversions with nicotine. These studies demonstrated that the time of drug administration can be as strong a determinant of place-conditioning effects as the drug itself.

Animals↗
PubMed1989

Evidence for a model of activation of central sigma systems.

Evidence for a drug-induced activation of central sigma systems is presented. The model is the locomotor activation initiated by a subcutaneous (SC) challenge of 1.6 mg/kg of (+)-butaclamol, (+)-BUT, given 30 min before 10 mg/kg SC of (-)-N-allylnormetazocine, (-)-NAN, in Sprague-Dawley male rats which have been pretreated with four daily injections of 10 mg/kg SC of (-)-NAN. The locomotor activation is characterized by an initial 20 min period of retropulsion and sideways-circling followed by 90 to 100 min of forward locomotion. The locomotor syndrome is antagonized by 10 mg/kg of (+/-)-BMY 14802, 20 mg/kg of rimcazole, and 0.2 mg/kg of haloperidol, but not by 0.04 mg/kg of R(+)SCH23390, 100 mg/kg of S(-)sulpiride, 10 mg/kg of naltrexone, or 2.5 mg/kg of MR2266. The data suggest that the manifestation of the (+)-BUT/(-)-NAN-induced syndrome depends upon intact transmission at central sigma sites.

Animals↗
PubMed1989

Antinociception after nicotine administration into the mesopontine tegmentum of rats: evidence for muscarinic actions.

The ability of nicotine to induce antinociception after subcortical administration was investigated in the rat. Adult male Sprague-Dawley rats were implanted unilaterally with guide cannulas aimed at the pedunculopontine tegmental nucleus of the mesopontine tegmentum. After 1 week, nicotine was injected in 0.5 microliter of 0.2 M pH 7.4 phosphate buffer. Antinociception was assessed using the 52 degrees C hot-plate test and the tail-flick method; for the most part, the results in the hot-plate test parallelled those in the tail-flick test. Nicotine inhibited nociceptive responses at a median effective antinociceptive dose (A5O) of 1.6 nmol in the hot-plate test and 3.4 nmol in the tail-flick test. Mecamylamine, 0.8 nmol coadministered with nicotine, antagonized nicotine antinociception as evidenced by 5- to 8-fold increases in the nicotine A5O. Nicotine antinociception was also antagonized by coadministrations of either 0.8 nmol of (-)-scopolamine or 0.4 nmol of the M1 antagonist pirenzepine by over 12-fold in the hot-plate test and 5-fold in the tail-flick test. The M2 antagonist methoctramine had antinociceptive effects of its own when injected into the mesopontine tegmentum at a dose of 0.1 nmol; when coinjected with nicotine, the effects of the methoctramine-nicotine combination appeared to be additive. One hour preinjection into the mesopontine tegmentum with 13.5 nmol of (-)-vesamicol, an agent which interferes with acetylcholine storage and/or release, markedly inhibited nicotine antinociception; only a 24% antinociceptive response could be elicited by nicotine in the hot-plate test whereas the nicotine A5O was increased 3-fold in the tail-flick test. Pretreatment with the inactive isomer (+)-vesamicol had no effect. In other experiments, mesopontine tegmental injection of (+)-cis-dioxolane, a high affinity muscarinic cholinergic agonist, elicited strong antinociceptive responses which were potently antagonized by coadministration with 0.5 nmol of pirenzepine but not by 0.8 nmol of mecamylamine. The data indicate that nicotine-induced antinociception may depend upon intact neurotransmission at M1 sites in addition to nicotinic sites within the mesopontine tegmentum.

Analgesia↗
PubMed1988

Actions of nicotine on the acquisition of an autoshaped lever-touch response in rats.

Experimentally naive male, Sprague-Dawley rats maintained at 85% of their original body weight were trained to touch a retractable lever that was presented on a random interval 48-s schedule. The lever retracted when touched or after 15 s had elapsed, and one 45 mg food pellet was delivered simultaneously with lever retraction or after an 8-s delay. Rats received ten daily sessions each consisting of ten lever presentations. Nicotine (0.25-0.8 mg/kg SC) administration, either 15 min prior to (pre-session) or immediately after (post-session) the daily autoshaping sessions, caused a significant dose-related impairment of acquisition with the post-session injections having the greater effect. Low doses of nicotine (0.025-0.1 mg/kg SC) had little effect on acquisition when injected pre-session or post-session. Injections of 0.45 mg/kg nicotine either immediately (t = 0) or at +5 min after the daily sessions impaired acquisition of the lever-touch response. Nicotine injected at +15, +30, +60, or +120 min had no effect on acquisition. A single intraventricular injection of the ganglionic blocker chlorisondamine (5 micrograms) 2 weeks prior to autoshaping blocked the impairment produced by 0.45 mg/kg nicotine. Post-session injections of nicotine did not alter the lever-touch behavior of well-trained animals, but suppressed responding in animals that were partially trained. Thus, nicotine-induced impairment of the autoshaped lever-touch response is dose dependent, centrally mediated, occurs within 5 min of a SC injection, and may interfere with post-training consolidation processes.

Animals↗
PubMed1988

Dynorphin A [1-17] induces "reward" in rats in the place conditioning paradigm.

Intracerebroventricular (i.c.v.) administration of dynorphin A [1-17] induced significant place preference conditioning in male, Sprague-Dawley rats. Place preferences were induced by 2.3 and 3.5 nmole, but not 1.2 nmole of dynorphin A. Co-administration of naloxone, 27.5 nmole but not 5.5 nmole, antagonized the reward response induced by 2.3 nmole of dynorphin A. Leu-enkephalin, 5 or 25 nmole, and dynorphin A [2-17], 2.3 or 3.5 nmole, had no effect in the place conditioning paradigm.

Animals↗
PubMed1988

Nicotine impairs acquisition of radial maze performance in rats.

The effects of nicotine (NIC) and scopolamine (SCOP) on radial maze acquisition were examined using an 8-arm radial maze. In Experiment 1, food-deprived Sprague-Dawley rats were trained to eat food pellets located at the ends of each arm of the radial maze without repeating arm choices. Both NIC (0.45 mg/kg, SC) and SCOP (0.25 mg/kg, IP) impaired acquisition when they were administered before, but not after the daily training sessions. Experiment 2 examined the effect of nicotine on working and reference memory in rats trained to a criterion of 3 correct choices out of the first 4 choices with only 4 of the 8 arms baited. NIC (0.1-0.45 mg/kg) had no effect on working memory (reentry into baited arms) or reference memory (entry into unbaited arms) errors. It is concluded that NIC impairs processes involved in the acquisition but not maintenance of radial maze performance. Neither NIC nor SCOP affects post-training consolidation processes.

Animals↗
PubMed1987

Conditioned aversion after delay place conditioning with nicotine.

Rats received subcutaneous injections of either nicotine (NIC; 0.05-0.8 mg/kg) or vehicle [VEH (phosphate buffer); 1 ml/kg] immediately after conditioning sessions in a place-conditioning paradigm (delay conditioning). NIC was paired for three delay-conditioning sessions with one environment of a three-compartment place-conditioning apparatus; VEH was paired with another environment. The subjects were then tested for place preference or aversion by determining the proportion of time spent in each compartment during a 15-min test session. Delay conditioning with NIC only produced a dose-related place aversion (greater time was spent in the VEH-paired chamber on test day). Place aversion was evident when NIC, 0.8 mg/kg, was administered either immediately or 5 min after conditioning sessions but not when given 15 min after conditioning. Chlorisondamine (5 micrograms, lateral ventricle), but not saline, administered 2 weeks prior to delay conditioning with 0.8 mg/kg NIC completely blocked the NIC-induced place aversion. These data suggest that delay conditioning with NIC produces place aversion by a central mechanism. Since standard conditioning (NIC injection immediately before the place-conditioning sessions) with NIC only produced dose-related place preferences (Fudala et al. 1985; Fudala and Iwamoto 1986), the time of administration of the unconditioned stimulus is a strong determinant of the place-conditioning effects of NIC.

Animals↗
PubMed1987

Studies on desglycinamide arginine vasopressin and scopolamine in a modified/lever-touch autoshaping model of learning/memory in rats.

Vasopressin administration has been reported to improve acquisition and retard extinction of both conditioned avoidance and food-reinforced behavioral tasks. In the present experiment the effects of a vasopressin analog (DGAVP) and scopolamine (SCOP) were tested in an autoshaped lever-touch model of learning and memory. Rats were food-deprived to 80% of original body weights and tested in modular cages which contained a retractable lever that was presented on a random interval 48 sec schedule. The lever retracted after 15 sec or when it was touched, at which time one 45 mg food pellet was delivered. Subcutaneous injection of 10 micrograms/kg DGAVP 1 hr prior to acquisition and extinction sessions did not alter responding compared to saline controls. DGAVP at doses of 10, 20, and 30 micrograms/kg also failed to affect responding in a more difficult task which included an 8 sec delay between lever retraction and reinforcement. Homozygous Brattleboro rats, which are deficient in vasopressin, did not differ from normal heterozygous littermates in the acquisition of the lever-touch response. Intraperitoneal injection of SCOP (0.1-0.8 mg/kg) 30 min prior to testing caused a dose-related impairment of acquisition compared to saline controls, but did not alter responding in animals which had previously acquired the lever-touch response. These data suggest that manipulations of vasopressin do not affect, while SCOP impairs, the acquisition of a positively reinforced lever-touch response in rats.

Animals↗
PubMed1986

Comparison of the pharmacologic effects of N-allylnormetazocine and phencyclidine: sensitization, cross-sensitization, and opioid antagonist activity.

The effects of phencyclidine (PCP) on locomotor activity were compared to those of the stereoisomers of N-allylnormetazocine (NAN) after acute administration to rats. PCP produced swaying and falling movements, increased sniffing behavior, and enhanced horizontal locomotor activity. d-NAN also induced swaying, falling, sniffing behavior and locomotion, and decreased rearing behavior. l-NAN decreased rearing activity, depressed locomotion, antagonized morphine antinociception and precipitated the morphine-withdrawal syndrome. Sensitization to drug-induced sniffing, rearing and locomotion developed after four daily injections of PCP, d-NAN or l-NAN in rats. Rats which were sensitized to PCP-induced locomotion, sniffing, and rearing were also cross-sensitized to both d-NAN and l-NAN. Animals sensitized to the effects of either d- or l-NAN exhibited cross-sensitization to PCP. There was little evidence that the cross-sensitization between the three agents was stereoselective. These data indicate that the acute effects of PCP are similar to those of d-NAN, but differ from l-NAN, the only agent of the three with opioid antagonist properties. The data further indicate that as sensitization to the motor effects develops during repeated administration of PCP, d-NAN or l-NAN, the differences among the three agents become less apparent.

Animals↗
PubMed1986

Further studies on nicotine-induced conditioned place preference in the rat.

Rats received subcutaneous (SC) injections of either nicotine (NIC, 0.001 to 2.0 mg/kg) or saline (SAL, 1 ml/kg) immediately prior to conditioning sessions in a conditioned place preference (CPP) paradigm. NIC was paired for 3 conditioning sessions with one environment of a 3 compartment CPP apparatus; SAL was paired with another environment. The animals were then tested for place preference by determining the proportion of time spent in each compartment during a 15 min test session. A dose-response curve was obtained for the place conditioning effect of nicotine as measured by its ability to alter baseline preferences calculated from control rats. NIC's place preference, but not place aversion, effect was linearly correlated with respect to dosage within the range of 0.1 to 0.8 mg/kg. NIC, 0.8 mg/kg, induced a place preference when it was administered immediately prior to conditioning sessions, but not when administered 20, 60 or 120 min prior to the sessions. Three repeated conditioning and testing cycles, or the daily administration of NIC for 2 weeks between conditioning and testing cycles had little or no effect on NIC place conditioning. Lobeline (2, 10 and 20 mg/kg) or cotinine (1 to 50 mg/kg) failed to condition a place preference. NIC, 0.1 or 1.2 mg/kg SC, administered to rat pups on postnatal days 5 through 8, did not alter subsequent place preference (induced by 0.8 mg/kg of NIC) measured at approximately 40 and 70 days of age. Periodic measurements of spontaneous motor activity, forelimb grip strength and negative geotaxis were unaltered by the perinatal exposure to nicotine.

Animals↗