Activation of CTP:phosphocholine cytidylyltransferase by hypochlorite-oxidized phosphatidylcholines

The acute psychomotor response and development of sensitization to amphetamine is attenuated if i.p. injections are given in the cage where a rat lives relative to when injections are given in a novel but physically identical test environment. Furthermore, when the environmental cues predicting i.p. injections are completely eliminated by using remotely activated i.v. injections in the home cage, 1.0 mg/kg amphetamine produces a very small acute response and no sensitization. The same treatments do produce sensitization if i.v. injections are signaled by placement of the rat in a novel test cage. The present experiment was designed to determine if there is a similar effect of environmental condition on the response to i.v. cocaine, and to what extent the effect may be dose-dependent. This was accomplished by comparing the psychomotor activating effects (rotational behavior) of repeated i.v. administrations of one of eight doses of cocaine (0.0, 0.3, 0.6, 1.2, 2.4, 3.6, 4.8, or 7.2 mg/kg) given in the home cage, with infusions of the same doses given in a novel test cage. There was no effect of environment on the acute psychomotor response to cocaine. There was, however, a significant effect of environment on the induction of sensitization. A higher dose of cocaine was required to induce sensitization when i.v. administrations were given in the home cage than when they were given in a physically identical but novel test environment. At high doses, however, cocaine induced sensitization regardless of environmental condition. The results suggest that the effect of this environmental manipulation is to shift the dose-effect curve for the induction of sensitization, and support the notion that the ability of psychostimulant drugs to induce sensitization can be modulated by the circumstances surrounding drug administration.     

Selective absorption of radio frequency energy due to collective motion of charged domains: case of lysozyme crystal

The role of the N-methyl-D-aspartate (NMDA) receptors in cocaine conditioning and sensitization of locomotor activity was studied in four groups of Sprague-Dawley rats. A sub-motoric dose of the NMDA antagonist MK-801 (0.1 mg/kg, i.p.) was employed using a novel dual-compartment Pavlovian drug conditioning paradigm. The animals were placed sequentially in two different test environments in which locomotor activity was monitored. In the first compartment, the animals always received a non-drug test for 20 min. Upon completion of this test, the animals received either saline, cocaine (10 mg/kg i.p.), MK-801 or MK-801 plus cocaine depending on group assignment and were then placed immediately into the second compartment and again tested for 20 min. A total of six non-drug and six drug tests were conducted every other day over a 12-day period. Across all drug/saline treatment and post-treatment tests for conditioning, there were no statistical differences in locomotor activity among the saline and drug treatment groups in the non-drug test environment. In the drug/saline associated environment, however, cocaine had a reliable stimulant effect on locomotion when administered alone or in combination with MK-801. Following a 1-day and again after 21-days of withdrawal, all animals were administered a non-drug test for conditioning in which no injections were administered. On both tests, all groups had equivalent activity levels in the non-drug environment. In the drug/saline environment, only the cocaine group of the three drug treatment groups exhibited conditioned hyperlocomotion. Importantly, MK-801 blocked conditioned hyperlocomotion in the combined cocaine+MK-801 group. MK-801 did not alter serum or brain cocaine concentration or the cocaine effects on dopamine metabolism in limbic brain tissue. The co-administration of MK-801 with cocaine, however, blocked the corticosterone release effect of cocaine. Thus, the NMDA receptor site appears critical for cocaine induced conditioning and for corticosterone release.     

Laryngeal tuberculosis and laryngeal cancer

The primary objective of this study was to determine whether the development of behavioral sensitization to the putative dopamine D3 receptor agonist 7-OH-DPAT could be prevented by either selective D1-type or D2-type dopamine receptor antagonists. In three experiments, male Wistar rats (250-350 g) were given seven to nine injections (at 48-h intervals) of 7-OH-DPAT (1.0 mg/kg, SC) or vehicle in combination with the D2-type dopamine antagonist eticlopride (0.3 mg/kg, SC), the D1-type dopamine antagonist SCH 23390 (0.1 or 0.2 mg/kg, SC), or vehicle. After the injections, the rats were tested for locomotor activity in photocell arenas for 2 h. In the first two experiments, after seven injections, all rats were tested for activity following vehicle injections to test for possible conditioning effects. In each experiment, after the last pre-exposure session, all rats were given a challenge injection of 7-OH-DPAT (1.0 mg/kg, SC) and tested for activity. Major findings were as follows: a) 7-OH-DPAT treatments produced a progressively greater increase in locomotor activity with repeated treatment; b) concurrent treatment with eticlopride or SCH 23390 (0.1 and 0.2 mg/kg) blocked the acute locomotor-activating effects of 7-OH-DPAT across days; c) eticlopride, but not SCH 23390, completely blocked the development of behavioral sensitization to 7-OH-DPAT. Although the low dose of SCH 23390 (0.1 mg/kg) produced a partial attenuation of sensitization, the higher dose (0.2 mg/kg) of SCH 23390 appeared to augment, rather than block, sensitization to 7-OH-DPAT; d) rats previously treated with SCH 23390 (0.2 mg/kg, but not 0.1 mg/kg) without 7-OH-DPAT displayed a hyperactive response to the 7-OH-DPAT challenge injection; and e) after vehicle injections, rats previously given 7-OH-DPAT, SCH 23390, or eticlopride either alone or in combination were more active than vehicle control rats. These findings suggest that the neurochemical mechanisms mediating the development of behavioral sensitization to 7-OH-DPAT may differ from those of other dopamine D2-type agonists such as quinpirole or bromocriptine. Moreover, these results demonstrate that hyperactivity responses following vehicle injections in drug-pretreated animals do not necessarily reflect conditioning mechanisms.     

Effects of administering cocaine at the same versus varying times of day on circadian activity patterns and sensitization in rats.

The effects of different schedules of cocaine administration on circadian activity patterns and locomotor sensitization were studied. Rats received intraperitoneal injections of either saline or 20 mg/kg cocaine at either 24- or 33-hr intervals for 8 cycles (development). After a 2-day withdrawal, they were given a cocaine challenge in a novel environment. Rats given cocaine at 24-hr intervals were hypoactive 4 to 9 hr postinjection during development and, during cocaine challenge, showed sensitization of locomotor activity. Rats given cocaine at 33-hr intervals did not show these effects. On the 33-hr-period schedule, activity was enhanced beginning 24 hr after drug receipt. Different intermittent schedules of cocaine receipt may alter the vulnerability to cocaine, and altered vulnerability may be more likely when a subsequent cocaine injection interacts with a distal state of sensitivity produced by a prior injection. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Proposed animal neurosensitization model for multiple chemical sensitivity in studies with formalin

A potentially promising line of animal research relevant to multiple chemical sensitivity (MCS) is that of sensitization in the central nervous system (CNS), particularly limbic pathways in the brain. Sensitization is the progressive and enduring enhancement in behavioral and neurochemical responses that occurs after repeated exposure to psychostimulants or environmental stressors. Since the onset and progression of sensitization has many parallels with that of MCS, it has been proposed that MCS may be initiated through a mechanism similar to the sensitization of CNS components occurring in the rodent. To test this hypothesis, female Sprague-Dawley rats were exposed to formalin vapors (FORM, 11 ppm) or water vapor (control) 1 h/day for 7 days. The next day, a saline injection was given followed by a cocaine injection (15 mg/kg, i.p.) 24 h later, and locomotor activity was monitored. Animals pretreated with repeated FORM inhalation demonstrated a significantly enhanced locomotor response to cocaine compared to controls, an indicator that specific limbic pathways may have been sensitized. At 4 weeks of withdrawal from FORM exposure, a subset of animals remained sensitized to a cocaine challenge. No differences were found between groups after a saline injection. In a second experiment, animals were screened prior to FORM or water exposure for their response to a novel situation, a measure believed to reflect an animal's general responsiveness to stimuli. Rats were divided into high responders (HR) or low responders (LR), based on their locomotion in a novel cage. Results from three behavioral tests demonstrated that HR and LR were differentially affected by exposure to FORM. In a passive avoidance test, HR and LR appeared to be different in their distribution of responses, while HR and LR responses in the FORM group were nearly identical. On the elevated plus maze test of anxiety, HR spent more time on the open arms than LR in both treatment groups, with significant differences between HR and LR in the FORM, but not water, treated group. On a hot plate test to measure nociceptive levels, no differences occurred between HR and LR in the control group, whereas nociception of LR tended toward an increase compared to HR in the FORM-exposed group. Results from the second experiment suggest that the effects of FORM exposure may be obscured by examining behavior in a heterogeneous population (HR and LR). This approach using animal models may help define neural substrates that mediate the amplification of responses of a subpopulation of individuals to chemicals in the environment.     

Modulation of cocaine- and methamphetamine-induced behavioral sensitization by inhibition of brain nitric oxide synthase

Evidence suggests the existence of multiple interactions between dopamine, glutamate and nitric oxide (NO) in brain structures associated with psychomotor stimulation. The present study was undertaken to investigate the effect of the relatively selective inhibitor of the neuronal nitric oxide synthase (NOS) isoform, 7-nitroindazole (7-NI), on the development of sensitization to the locomotor stimulating effect of cocaine and methamphetamine (METH). Male Swiss Webster mice that received 15 mg/kg cocaine once a day for 5 days developed a marked locomotor sensitization to a challenge cocaine (15 mg/kg) or cross-sensitization to a challenge METH (0.5 mg/kg) injection given after a 10-day drug-free period. This treatment also produced a context-dependent sensitization as evident by the sensitized response to a challenge saline injection. Pretreatment with 7-NI (25 mg/kg) 30 min before cocaine administration (5 days) completely blocked the induction of sensitization to cocaine, the cross-sensitization to METH and the conditioned locomotion induced by cocaine. 7-NI when given alone, either acutely or for 5 days, had no significant effect on the locomotor activity of animals. Animals treated with METH (1.0 mg/kg) for 5 days developed marked sensitization to challenge METH (0.5 mg/kg), cross-sensitization to challenge cocaine (15 mg/kg) and context-dependent locomotion. Pretreatment with 7-NI (25 mg/kg) attenuated the sensitized response to METH and the cross-sensitization to cocaine as revealed after a 10-day drug-free period. However, the METH-induced conditioned locomotion was unaffected by the pretreatment with 7-NI. The present study supports the role of brain NO in the development of sensitization to both psychostimulants, cocaine and METH. However, it appears that the inability of 7-NI to completely abolish the sensitized responses induced after METH administration is the result of the resistible conditioned locomotion caused by METH, but not by cocaine.     

Immune function alterations in mice tolerant to delta9-tetrahydrocannabinol: functional and biochemical parameters

The present study examined (1) whether the neostriatum is involved in a drug-induced conditioned locomotor response and; (2) whether this structure participates in the development of behavioral sensitization. Moreover, the present study addressed the question whether the development of behavioral sensitization is necessary for the induction of conditioning. Rats received injections of either apomorphine (2 microg) or vehicle (solution of 0.1% ascorbate/saline) into the dorsal neostriatum daily for 7 days. These treatments were performed immediately prior to (apomorphine-paired group and vehicle group) or 30 min following (apomorphine-unpaired group) 10-min placement in an open field which served as the test environment. After a 3-day drug withdrawal period, the animals were given a 10-min non-drug vehicle test trial in the test environment. Three days later, a drug test with apomorphine was administered to the animals of the paired and unpaired treatment groups; the vehicle group again received an injection of vehicle. The analysis of locomotor activity in the open field (measured as the distance traversed) revealed that locomotor activity in the apomorphine-paired group was higher than in the other groups. There were no indications for behavioral sensitization to intrastriatal apomorphine, since the locomotor response in the apomorphine-paired group did not increase, but rather decreased with daily repeated injections of apomorphine. Furthermore, only the apomorphine-paired animals showed a higher locomotor response when tested after an intrastriatal injection of vehicle in the previously apomorphine-paired environment, which is indicative of a conditioned drug effect. These results suggest that the neostriatum is directly involved in the development of drug-induced conditioning of locomotor behavior but not in the establishment of behavioral sensitization.     

Wheel-running behavior is altered following withdrawal from repeated cocaine in adult rats.

The residual effects on open-field habituation and self-generated wheel running following withdrawal from repeated cocaine (COC; 30 mg/kg for 7 days) were examined in adult male rats. Control subjects received equivolumetric injections of saline (SAL) and were either allowed to feed ad libitum or pair-fed matched (PF SAL) to COC subjects to control for the drug's potential anorexic effect. Following 10 days of withdrawal, all subjects were examined twice on each of the two assessment instruments. Results indicated that COC subjects over the two test sessions failed to increase their wheel-running rates and did not show the expected habituation in the open field. However, because both COC and PF SAL groups yielded similar effects in the open field, conclusions about cocaine's consequences on habituation could not be established independent of the drug's anorexic effect. These data provide evidence for the view that repeated cocaine impairs motivational processes responsible for engaging in self-generated naturally rewarding behaviors. Speculation concerning the neurobiobehavioral substrates for this effect is presented. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Conditioning and experiential factors affecting the development of sensitization to apomorphine.

In 3 experiments, the role of conditioning and experiential factors in producing behavioral sensitization to apomorphine (APO) was examined. In each experiment, male rats received intermittent injections of APO (5.0 mg/kg s.c.) or vehicle and were tested for locomotor activity in photocell arenas. Activity test experience was paired or unpaired with drug exposure or not given. After the pretreatment phase in each experiment, all rats were tested for activity after an APO injection. The results indicated that behavioral sensitization to APO develops with repeated treatments in the absence of drug-associated contextual environmental stimuli. The magnitude of the sensitization effect observed, however, was always greater in rats for which specific environmental cues were reliably associated with drug exposure. These findings indicate that behavioral sensitization to APO develops through both associational and non-associational mechanisms. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Conditioning of and contextual sensitization to apomorphine-induced climbing in mice: Evidence against the habituation hypothesis.

Several predictions of the habituation hypothesis of conditioned drug effects were tested by looking at contextual sensitization to apomorphine-induced climbing in mice (Mus musculus). Mice were first sensitized to that effect after 9 daily injections of 0.4 mg/kg apomorphine in the test context. Other mice received the same treatment outside the test context. On Day 10, all mice were challenged with either saline (conditioned drug effects test) or apomorphine (contextual sensitization test). On both tests, the levels of climbing of mice that received apomorphine paired with the test context during the intermittent treatment were significantly higher than those of mice that were experiencing the test context for the first time (unexposed mice). Also, the rate of extinction in conditioned mice did not parallel the rate of habituation in the unexposed mice. Results contradict the habituation hypothesis of conditioned drug effects and contextual sensitization. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Repeated injection of GBR 12909, but not cocaine or WIN 35,065-2, into the ventral tegmental area induces behavioral sensitization

A role for the mesolimbic dopamine system in the development of behavioral sensitization to psychostimulants, such as cocaine and amphetamine, is well established. Previous reports have suggested that the ventral tegmental area (VTA) is involved in the initiation of, while the nucleus accumbens is in involved in the expression of behavioral sensitization. This hypothesis is supported in part, by studies which demonstrated that behavioral sensitization could be induced by repeated intra-VTA, but not intra-accumbal, administration of amphetamine. The present studies were designed to determine whether repeated intra-VTA cocaine would similarly induce behavioral sensitization. Rats receiving four daily injections of cocaine (1.5, 5 or 15 nmol/side) into the VTA did not show a sensitized behavioral response when challenged with cocaine (15 mg/kg, ip) 1 week later. In contrast to this, repeated injection of the specific dopamine reuptake inhibitor, GBR 12909 (15 nmol/side) produced behavioral sensitization to a challenge injection of cocaine. Repeated injections of the cocaine analog WIN 35,065-2 did not induce behavioral sensitization to cocaine, suggesting that the local anesthetic properties of cocaine were not responsible for the inability of intra-VTA cocaine to induce sensitization. In summary, the data suggest that sensitization to cocaine may involve mechanisms different from amphetamine.     

Prenatal exposure to cocaine: effects on aggression in Sprague-Dawley rats

Social/aggressive behavior in adult rat offspring (beginning at postnatal Day 180) prenatally exposed to saline, cocaine, or amfonelic acid (AFA) was examined. Pregnant rats received injections of 15 mg/kg of cocaine, or 0.9% saline twice daily, s.c., or on 2 consecutive days at 4-day intervals, or 1.5 mg/kg amfonelic acid daily throughout gestational Days 1-20. Frequency, duration, and latency of 11 social/aggressive behaviors were recorded for two 15-min sessions during which a smaller male intruder replaced an ovariectomized female in the resident's home cage. Subjects received a s.c. saline injection before Session 1 and 2.0 mg/kg of gepirone, a 5HT1a partial agonist, prior to Session 2. Prenatal cocaine treatment resulted in alterations of aggressive behavior. Aggressive behavior was reduced by gepirone in all groups but to a lesser extent in the AFA group.     

A simple slide-rule method for the assessment of renal tubular reaborption of phosphate in man

Twenty-five male Sprague-Dawley rats were trained in five two-lever operant chambers on a DRL-15 sec schedule of positive food reinforcement to discriminate 10 mg/kg cocaine from 1 ml/kg saline. Following acquistions of discrimination a counterbalanced design of extinction tests was performed before and after repeated administration of 20 mg/kg cocaine or saline (three times a day at five hr intervals for seven days). The extinction tests consisted of testing responses of animals following 1 ml/kg saline, 2.5 mg/kg cocaine, or 5 mg/kg cocaine. The results showed no significant difference in animals' level choice before and after repeated injection with saline. However, the percent cocaine lever choice with the two doses of cocaine was lower after repeated administration of cocaine than before the repeated injections. This indicates tolerance developed to the discriminative stimulus properties of cocaine.     

Amphetamine-induced conditioned activity and sensitization: the role of habituation to the test context and the involvement of Pavlovian processes

Behaviours associated with drug action can sometimes be elicited, in the absence of drug, by exposure to stimuli that were present during drug administration. Such a finding is usually interpreted as a conditioned drug effect. Often, however, the outcome could arise if drug administration in a particular environment retarded behavioural habituation to that environment. To test the 'habituation hypothesis' of conditioned drug effects, mice received 10 daily injections of d-amphetamine ('paired' group) or saline ('unpaired') in test boxes, and the converse injections in the colony room. Another group received saline in both environments. The apparatus and procedures yielded minimal habituation of behaviours (ambulation and rearing) over sessions. Only the paired group demonstrated behavioural sensitization, indicating environment-specific sensitization. The paired group also showed more ambulation and rearing than the others on the critical test of conditioning (saline injection in test box); moreover, their conditioning test scores were higher than those of the other groups on their first exposure to the test boxes, contradicting the habituation hypothesis. Further supporting the involvement of Pavlovian conditioning, levels of ambulation and rearing measured for 10 min before each injection increased in the paired group, relative to the unpaired groups, over successive pairing sessions. Tests controlling for differential handling/injection experience produced results consistent with those previously obtained. Together, the findings are incompatible with the habituation hypothesis, and further support the role of Pavlovian conditioning.     

Increased sensitivity to the locomotor depressant effect of a dopamine receptor antagonist during cocaine withdrawal in the rat

The effect of a dopamine receptor antagonist on locomotor activity was examined during withdrawal from either self-administered or experimenter-administered cocaine. In the self-administration experiment, the locomotor response to a challenge injection of cis-flupenthixol was assessed in photocell cages at 4 h after the cessation of a 12-h cocaine self-administration session. Rats which had self-administered cocaine, and were challenged with cis-flupenthixol (0.05 mg/kg), were found to be hypoactive relative to controls. In the experimenter-administered cocaine experiment, animals were given eight IP injections of 15 mg/kg cocaine over a 9.5-h period, for a total of 120 mg/kg. At 4, 8, and 24 h (tested in three separate groups of rats) after cessation of the eight injections, the locomotor response to a challenge injection of saline or cis-flupenthixol was tested. Cocaine-treated animals displayed a dose-dependent, heightened sensitivity to the locomotor depressant effects of 0.05 mg/kg and 0.2 mg/kg cis-flupenthixol 4 h post-cocaine, whereas they did not show increased sensitivity to 0.05 mg/kg cis-flupenthixol 8 or 24 h post-cocaine. However, cocaine-treated animals displayed a mild hypoactivity 8 h post-cocaine. In a separate group of animals, a dose-response experiment was performed which indicated that a dose of cis-flupenthixol as high as 0.2 mg/kg was required to produce locomotor depression in cocaine-naive rats. The results of this study support clinical observations of dopamine antagonist-precipitated motor dysfunction in abstinent cocaine abusers, and lend further support to the hypothesis that alterations in dopaminergic neurotransmission consequent to prolonged cocaine exposure are partly responsible for some of the symptoms of cocaine withdrawal.     

Repeated cocaine augments excitatory amino acid transmission in the nucleus accumbens only in rats having developed behavioral sensitization

Rats were pretreated with daily cocaine or saline injections for 1 week. The rats treated with daily cocaine were separated into two groups: a sensitized group of animals demonstrating > 20% increase in motor activity on the last injection compared with the first injection of daily cocaine, and a nonsensitized group showing < 20% elevation. At 2-3 weeks after the last daily injection, four experiments were performed to assess changes in excitatory amino acid (EAA) transmission in the nucleus accumbens produced by repeated cocaine administration. (1) Rats were challenged with a microinjection of AMPA into the shell or core of the nucleus accumbens. The sensitized rats demonstrated greater motor activity than did the saline-pretreated or nonsensitized animals after AMPA injection into either subnucleus. (2) It was shown that the behavioral distinction between sensitized, nonsensitized, and control rats in behavioral responsiveness to AMPA was not mediated by differences in AMPA-induced dopamine release. (3) The extracellular content of glutamate was measured after a cocaine challenge given at 21 d of withdrawal. Cocaine elevated the levels of glutamate in the core of sensitized rats, but not of nonsensitized or control rats. (4) Microinjection of the non-NMDA antagonist 6-cyano-7-nitroquinoxaline-2,3-dione into the core abolished the augmented motor response to a cocaine challenge in sensitized rats, but was without effect on cocaine-induced motor activity in nonsensitized animals. These results indicate that repeated cocaine administration increases EAA transmission in the nucleus accumbens only in rats that develop behavioral sensitization to cocaine.     

Changes of behavior and monoamine metabolites in the rat brain after repeated methamphetamine administration: effects of duration of repeated administration

1. The authors studied the mechanism of the reverse-tolerance phenomenon caused by long-term administration of central stimulant drugs. Methamphetamine(MAP) was chronically administered to rats, and the reverse-tolerance phenomenon was studied in terms of behavioral changes and changes in monoamine metabolites, the latter being examined by in vivo microdialysis of the extracellular compartment of the corpus-striatum. The authors also studied [3H]SCH23390 and [3H]spiperone binding to striatal membranes after chronic MAP administration. 2. MAP(4 mg/kg) or saline was administered intraperitoneally once daily to male rats. In Groups 1 and 2, 10 and 30 injections of MAP were given, respectively. In Groups 3 and 4, animals received 10 and 30 injections of saline as controls. One week after the final injection, all rats were challenged with 4 mg/kg MAP. 3. Groups 1 and 2 displayed more intense stereotypy than Groups 3 and 4, indicating that behavioral sensitization had been achieved in the former. Dopamine(DA) levels increased rapidly in response to MAP challenge in all groups, with the increases in Groups 1 and 2 being more marked than that in Groups 3 and 4. Group 1 showed greater persistence and a higher rate of DA increase than Group 2. 4. The number of D1 and D2 dopamine receptors did not change after the repeated MAP administration. 5. The rate of increase in DA release induced by MAP was dependent on the duration of repeated administration, and there was no correlation between the intensity of stereotypy and the rate of increase in DA release induced by MAP. These findings suggest that enhancement in DA release is unlikely to be the sole cause of behavioral sensitization.     

The results of inferior and middle meatal antrostomy under endoscopic control

This study examined the extent to which chronic d-amphetamine administration sensitizes animals to some behavioral and neurochemical effects of foot shock stress. Rats received daily injections of saline for 14 days or d-amphetamine (2 mg/kg 7 days and 4 mg/kg 7 days). After a 7 day drug abstinent period, extracellular dopamine, 3,4-dihydroxyphenylacetic acid and homovanillic acid concentrations were measured in the medial prefrontal cortex using in vivo microdialysis in freely moving rats. The behavioral responses to mild foot shock stress were enhanced in the d-amphetamine-pretreated subjects. Concomitant with this behavioral sensitization, d-amphetamine-pretreated subjects showed greater stress-induced increases in extracellular dopamine in the medial prefrontal cortex than in controls. d-Amphetamine (2 mg/kg)-induced stereotyped behavior was also enhanced in the amphetamine-pretreated animals compared to controls; however, d-amphetamine-induced increases in extracellular dopamine in the medial prefrontal cortex were not enhanced in the amphetamine-pretreated group. These results suggest that the mesocortical dopaminergic system is involved in cross-sensitization between d-amphetamine and stress, but not in d-amphetamine-induced behavioral sensitization.     

Latent sensitization to apomorphine following repeated low doses.

In 2 experiments, the effect of repeated injections of apomorphine on locomotor activity of rats was determined. In each experiment, different groups of rats were injected with either apomorphine (0.2, 1.0, or 5.0 mg/kg) or vehicle at either 24 or 72 hr intervals and tested for locomotor activity in photocell arenas. In Exp II, following 13 treatment sessions with various doses, all groups were first tested for activity following a 5.0 mg/kg dose of apomorphine and then given vehicle only prior to the final activity test session. Major findings were as follows: (a) repeated injections of 1.0 and 5.0 mg/kg apomorphine produced a progressively greater increase in activity with each injection (i.e., sensitization); (b) injections of 0.2 mg/kg of apomorphine produced a slight inhibition of activity, which did not change with repeated injections; (c) prior treatment with 0.2 mg/kg of apomorphine resulted in a significantly greater activity increase following a 5.0 mg/kg dose of apomorphine than did prior vehicle treatments; and (d) chronic pretreatment of rats with apomorphine did not affect their activity level following a vehicle injection. Findings suggest that sensitization to apomorphine is a graded, rather than an all or none, phenomenon dependent on the dose of apomorphine repeatedly administered. In addition, results are inconsistent with autoreceptor tolerance and conditioning explanations of dopamine agonist-induced sensitization effects. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Elements in the choice of a technic for female sterilization]

This experiment determined whether overt performance of the entire response (actual running) was necessary for the conditioning of methylphenidate-induced locomotor activity (wheel-running) in guinea pigs. Four guinea pigs were given daily injections of 2.5 mg/kg methylphenidate and were allowed to run in activity wheels; 4 other guinea pigs were given methylphenidate and were placed in locked activity wheels; a third group of 4 guinea pigs were administered saline and allowed to locomote; a fourth group of 4 guinea pigs received saline injections and were placed in locked activity wheels. After 12 days of injection, all animals were given saline injections on the 9 subsequent days and allowed to run freely in the wheels. The 2 groups which had received methylphenidate showed more locomotor activity than the saline injected animals but were not distinguishable from each other on the basis of prior opportunity to engage in locomotor activity. These results were interpreted to indicate that (a) increased methylphenidate-induced locomotor activity may be conditioned with repeated administration of the drug, and (b) actual running is not essential for the conditioning of drug-induced wheel-running.