S.N. Pradhan

Behavioural and neurochemical effects of repeated administration of cocaine in rats

Abstract The effects of repeated administration of cocaine (15 mg/kg, i.p. twice daily at 8-hr intervals) were investigated on the spontaneous motor activity (SMA) and stereotypy (ST) as well as on the various neurotransmitters (e.g. norepinephrine, NE; dopamine, DA; serotonin, 5-HT; acetylcholine, ACh) in different brain areas (e.g. diencephalon-midbrain, DM; pons-medulla, PM; caudate nucleus, CN) in rats. Following repeated injections of cocaine, both SMA and ST gradually increased, reaching a peak in each case on about the 9th day, then gradually decreased up to the 18th or 20th day, after which the activities were maintained at minimum level which was slightly higher than normal levels. Concomitantly, the DA level in the CN and DM increased and 5-HT in the DM and PM decreased reaching their maximum or minimum levels following cocaine injections on the 9th day; these changes were gradually minimized by the 18th day and remained so up to the 30th day. There were also slight changes in NE and ACh levels. It thus appears that, following repeated cocaine administrations, the changes in the drug-induced behavioural effects can be correlated roughly with the changes in the DA level in the CN and the 5-HT levels in the DM and PM.

Correlation of behavioral and neurochemical effects of acute administration of cocaine in rats

Abstract Effects of cocaine were investigated on spontaneous motor activity (SMA) and stereotypy as well as on the concentrations of norepinephrine (NE), dopamine (DA), serotonin (5-HT) and acetylcholine (ACh) in the discrete brain areas, such as the caudate nucleus (CN), diencephalon-midbrain (DM) and pons-medulla (PM) in rats up to 90–120 min following its injection in single doses (15–20 mg/kg, i.p.). After cocaine administration, the SMA was increased usually reaching its peak between 10–20 min, and then decreased gradually. Stereotypy and its components gradually increased to their maximum at about 50–60 min and remained at that level during rest of 120 min sessions. NE levels slightly increased in the DM and PM at 10 min post-drug after which they were decreased at 20 min. DA levels in the CN and DM were increased markedly at 20 min post-drug and decreased at 40 min. 5-HT levels in DM and PM decreased gradually up to 20 min, then began to increase. ACh level in the CN was gradually increased at 40 min and then decreased. It appears that cocaine-induced hyperactivity and stereotypy followed release of NE and DA after their accumulation in the respective brain areas.

Phencyclidine (PCP): Some human studies

Studies on the effects of PCP have been conducted in volunteers in the Army Laboratories and elsewhere and in illicit users. The present review has summarized the observations of many investigators which showed that the acute effects of PCP following several routes of administration were shown to be dose-related. High doses of PCP produce disturbing manifestations including psychosis, numbness, light-headedness, vertigo, ataxia, and nystagmus due to acute intoxication. Furthermore, some subjects became irritable, argumentative or negative under the conditions of social stress and demanding tasks. In addition to a variety of central action, PCP has also been shown to affect cardiovascular function, heat storage, and exercise performance. PCP can also induce, although rarely, prolonged toxic psychosis in chronic abusers and precipitate psychotic episodes in psychotic and prepsychotic personalities. Tolerance, but not physical dependence, develops to the effects of PCP. Psychologic dependence as indicated by craving for the drug has however been reported.

Behavioral and neurochemical effects of Δ9-tetrahydrocannabinol in rats

Abstract Effects of Δ 9 -tetrahydrocannabinol (Δ 9 -THC) were studied on self-stimulation (SS) behavior in rats with electrodes implanted at either the posterior hypothalamus (PH) or area ventralis tegmentum (A10 area). Its effects were also studied on spontaneous motor activity (SMA), rectal temperature, barbiturate sleeping time, and neurotransmitter levels in discrete brain areas. Two patterns of Δ 9 -THC effects were observed in these experiments. One type consisted of gradual depression persisting over a prolonged period. Hypothermia, potentiation of barbiturate-induced sleep and decrease in SS responding to nonaroused subjects, are examples. These effects may be due to a generalized central depression. The other type, a triphasic effect, is characterized by an initial depression followed by a stimulation and then again depression, and was observed in SS in aroused subjects and also in SMA. The effects of the psychomotor stimulants (such as amphetamine and cocaine) were antagonized during the initial depressant phase and unaffected or even potentiated during the subsequent stimulant phase. The neurochemical studies demonstrated an initial decrease of dopamine (DA) levels in the caudate nucleus and diencephalon-midbrain (DM) and an increase of serotonin (5-HT) in DM and pons-medulla (PM) followed by an increase of DA and a decrease of 5-HT levels, and then their return to near normal levels in respective brain areas. These changes in neurotransmitter levels appear to be correlated to the triphasic behavioral effects.

Effects of toluene exposure on the spontaneous cortical activity in rats

Effects of toluene on the electroencephalogram (EEG) and its power spectra were measured during a 2-hr exposure in a dynamic inhalational chamber in rats. Rats were exposed to one of six graded concentrations (110.6, 162.5, 432, 676, 1558, 2730 ppm) of toluene on different days. It was found that the duration of waking (W) was increased with a decrease in duration of rapid eye movement (REM) sleep even at 110.6 ppm. Duration of nonrapid eye movement (NREM) sleep was decreased with an increase of W and a decrease of REM sleep at 162.5 ppm. Dose-related effects were noted in higher concentrations. The power of delta frequency band was increased with a decrease of theta frequency band power at hr 1 of exposure to 676 ppm during REM sleep recorded from the visual cortex. The power of theta frequency band was also decreased at hr 2 of exposure at 432 ppm. During W and NREM sleep power spectra were not changed significantly. Results indicate that the changes of EEG are a sensitive measure of the effects of toluene on the central nervous system (CNS).

An inhalational behavioral chamber

An inhalational (flow-through) behavioral chamber has been designed and prepared in order to facilitate recording of the behavioral performance of a small experimental animal (e.g., rat and mouse) while the subject is being exposed to an inhalant (vapor or gas). The animal can be clearly viewed during behavioral performance inside the chamber, which consists of a cylindrical glass jar. The apparatus is made up of easily available materials (e.g., glass, metal, Teflon, etc.) that are not affected by usual industrial solvents. At the present stage of its development, three types of behavioral schedules can be performed within the chamber: schedules involving brain stimulation (e.g., self-stimulation, avoidance of aversive stimulations); liquid-reinforced schedules (e.g., fixed ratio, fixed interval, variable ratio, variable interval, differential reinforcement of low rates); shock avoidance (classical or continuous). The schedules can be microcomputer assisted. The device is suitable for study of behavioral pharmacology and toxicology of inhalants.

Interaction of self-stimulation and ethanol-intake behaviors in rats.

Abstract The effect of ethanol (10% v/v) intake was studied on the rate of self-stimulation (SS) in rats implanted with bipolar electrodes in the posterior hypothalamus. The rats were divided into 3 groups: in Group A, 6 rats were trained to press a bar for SS, and allowed to drink water only; in Group B, 6 rats were trained also for SS, and in Group C, 5 rats were put on to rotarod performance and served as controls for the physical exercise incurred in SS schedule; rats of both Groups B and C were offered ethanol and water in free choice. At the termination of the experiment, the contents of norepinephrine (NE) and serotonin (5-HT) in diencephalon-midbrain (DM) and pons-medulla (PM), and dopamine (DA) contents in DM and caudate nucleus (CN) of these rats were estimated. While in Group A rats the SS rate decreased gradually, in Group B rats the SS rate increased significantly and their ethanol intake increased to approximately 60% of their total fluid intake (TFI). In Group C rats ethanol intake was low (about 30% of TFI), compared to Group B. Neurochemical studies in Group B and C showed increased NE and 5-HT contents in DM and PM and decreased DA contents in CN and DM, compared to controls. The interaction between the two reinforcing behaviors seems to be related to induced changes in the brain amines.

Actions and interactions of amphetamine on self-stimulation in rats

The dose-response relationship for d-amphetamine (0.125-2 mg/kg, IP) and its l-isomer (0.125-3 mg/kg, IP) was studied in self-stimulation behavior of rats each with an electrode at posterior hypothalamus (PH, mainly monoaminergic) or area ventralis tegmentum (A10, dopaminergic). The drug effects increased with the dose reaching a peak (at 0.5 mg/kg with d-amphetamine and at 1.0 mg/kg with 1-amphetamine) and then decreased. The d-isomer was approximately twice as potent as the l-isomer in enhancing intracranial self-stimulation (ICSS) rate with electrodes at either site. Azaperone (mainly an alpha-adrenergic blocker) and haloperidol (an antidopaminergic neuroleptic) used in small doses (0.05 and 0.008 mg/kg respectively) which did not affect the baseline responding, blocked amphetamine-induced enhancement of ICSS in both groups of rats. Thus, amphetamine-induced facilitation of ICSS at both PH and A10 areas and its blockade by an alpha-adrenergic blocker as well as an antidopaminergic neuroleptic show the involvement of both noradrenergic and dopaminergic mechanisms in self-stimulation behavior.