The effects of cocaine and d-amphetamine, two psychomotor stimulant drugs with pronounced addictive properties, on the electroencephalogram (EEG) of rats were studied by telemetric recordings from the skull in non-anesthetized, freely moving rats. The electrocorticogram (ECoG) was recorded. Both cocaine (10 mg/kg IP) and d-amphetamine (0.4 mg/kg IP) produced a desynchronization, characterized by a general lowering in power in all of the frequency bands. These effects of both drugs were mimicked by the selective agonist at D1 receptors SK&F 38393 (3 mg/kg SC) and were reversed by the antagonist at D1 receptors SCH 23390 (0.2 mg/kg IP) but not influenced by haloperidol (0.1 mg/kg IP) in a dose which is likely to block D2 rather than D1 receptors. These doses of cocaine or d-amphetamine did not produce stereotyped behaviour and slight, if any, increases in locomotor activity only. Large doses of cocaine (30 mg/kg IP) or d-amphetamine (4 mg/kg IP) produced stereotyped behaviour and alterations in EEG which are, based on previous own studies, characteristic for additional stimulation of D2 receptors. This was manifest in a selective increase in power of the alpha-1 band. A similar effect was also produced by the agonist both at D1 and D2 receptors, apomorphine (0.5 mg/kg SC). These results suggest that moderate, but probably rewarding doses of cocaine or d-amphetamine mainly activate D1 dopamine receptors. This activation might be relevant for the rewarding properties of these drugs.

The effects of a stimulation of dopamine D1 receptors by using (±)SKF 38393 on the cortical EEG in rats which were chronically implanted with electrodes were studied. Administration of SKF 38393 (3 or 9 mg/kg, s.c.) produced alterations suggesting an arousal in the EEG: the power in all of the frequency bands decreased to a level of 70–80% of baseline activity, which effect was dose- and time-dependent. In behaviour, episodes of intensive grooming (face-washing) alternated with those of lack of spontaneous motility and occasionally chewing movements were noted. In contrast, apomorphine (0.5 mg/kg, s.c.) produced a selective increase in power in the α1 band, accompanied by stereotyped sniffing and licking. The effects of SKF 38393 (9 mg/kg) were completely blocked by pretreatment with the selective antagonist at D1 dopamine receptors, SCH 23390 (0.2 mg/kg, i.p.). The application of haloperidol (0.1 mg/kg, i.p.), which is mainly a D2 blocker, failed to influence the alterations induced by SKF 38393 (9 kg/kg, s.c.). In a further experimental group, the effects produced by stimulation of D1 receptors (SKF 38393 9 mg/kg), followed by activation of putative dopamine autoreceptors by a small dose of apomorphine (0.05 mg.kg, s.c.) were studied: in this case, the effects of SKF 38393 were abolished and typical effects of small doses of apomorphine were manifest, such as hypokinesia and sedation, accompanied by large increases of power in all of the frequency bands, except β2. The results suggest that stimulation of D1 receptors produces some desynchronization in the EEG. Obviously, two different treatments, which are both expected to decrease activation of postsynaptic D2 receptors (haloperidol by blockade of the receptors or small doses of apomorphine, by a decrease in release of dopamine), interacted with stimulation of D1 receptors in a completely different way. This observation casts doubt on the hypothesis that behavioural and EEG effects, produced by apomorphine in a small dose, are due to activation of D2 autoreceptors.

Previously, in own studies, it was shown that stereotyped behaviour produced by apomorphine can be conditioned if the drug is repeatedly paired with defined environmental stimuli (conditioned stimuli, CS). Eventually, the presentation of CS alone produces stereotyped behaviour as conditioned response (CR). Furthermore, in electrocorticographic recordings it could be demonstrated that the characteristic pattern following acute apomorphine treatment, namely a selective increase in the power of the alpha-1 band, could be conditioned as well. In the present study, regional EEG was recorded in the striatum and in the hippocampus of freely moving rats. For conditioning, apomorphine (0.5 mg/kg s.c.) was paired with auditory and olfactory stimuli as CS for seven times, and on the eighth day the drug was substituted by the solvent in the presence of the CS. The effects were compared with those obtained in "pseudoconditioned" controls. Acute apomorphine administration led to an increase in power in the alpha-1 band (7.00-9.50 Hz), which effect was obvious in the hippocampus, above the cortex and in the striatum. After performing the conditioning procedure, these effects in regional EEG were found to be conditioned as well: as CR, activation in power in the alpha-1 band in hippocampus and striatum were manifest in the presence of the CS, but in absence of the drug. These effects occurred sporadically, but with a significantly higher frequency than in the pseudoconditioned controls. The results suggest that both the hippocampus and the striatum play important roles in classical conditioning of apomorphine effects which are primarily mediated by the striatum.

Alterations in cortical EEG activity in male rats produced by putative agonists at dopamine (DA) autoreceptors and by antagonists at postsynaptic DA receptors were compared in order to study, whether an impairment in dopaminergic neurotransmission via two different mechanisms might result in similar or different effects. Simultaneously to the EEG recordings, gross behaviour was observed. Putative agonists at DA autoreceptors (apomorphine 0.05 mg/kg, quinpirole 0.05 mg/kg, or talipexole 0.02 mg/kg s.c.) produced increases in the power iin all of the frequency bands, except beta-2, with the most pronounced increase in the delta band. These EEG alterations were accompanied by hypokinesia, ptosis and yawning. In contrast, antagonists at DA receptors (haloperidol 0.1 mg/kg i.p., D2 blocker) or SCH 23390 (0.2 mg/kg i.p., D1 blocker) led to little increases in the delta band, but more pronounced increases in the alpha-2 band. Behavioural signs were hypokinesia, but little ptosis and yawning. The combination of both blockers produced, in addition, strong increases in the delta band and behavioural signs of ptosis and yawning. These results suggest that activation of putative dopamine autoreceptors produced EEG patterns and behavioural patterns different from those produced by blockade of either D1 or D2 postsynaptic dopamine receptors. In contrast, the effects following a stimulation of putative DA autoreceptors, which are expected to decrease the release of the agonist and its action at postsynaptic D1 and D2 receptors, were very similar to those found after a combined blockade of both types of postsynaptic dopamine receptors.

Alterations both in the activity of the cortical EEG and behaviour were studied after administration of dopamine receptor agonists. In addition to apomorphine, which provided contrasting effects, both on the EEG and behaviour, when small and large doses were compared, alterations elicited by the D2 agonist, quinpirole and another agonist, with preference for dopamine D2 autoreceptors, talipexole (B-HT 920), were evaluated by using telemetric EEG recordings in rats.Similarly to apomorphine, quinpirole produced opposite effects after small and large doses: a small dose (0.05 mg/kg) led to sedation and an increase of EEG power spectra in all of the bands, except beta2, whereas a larger dose (0.5 mg/kg) elicited stereotypy and desynchronization of the EEG, with a characteristic increase of power in the alpha1 band.The effects on the EEG and on behaviour, obtained with the small dose of quinpirole were very similar to those of a small dose of apomorphine (0.05 mg/kg) and a small dose of talipexole (0.02 mg/kg) but even the large dose of talipexole (0.5 mg/kg) produced similar effects: all of these treatments produced behavioural sedation and an increase of power in the EEG in all of the bands, except beta2; such increases appeared most pronounced in the delta band.The present study provides further evidence that drugs, which are assumed to activate dopamine autoreceptors, are effective in inducing sedation. This sedation was accompanied by a characteristic pattern, observed in EEG power spectra analysis.

The possible conditioning of pharmacological effects of apomorphine on the electroencephalogram was studied using telemetric recordings in rats. Previous studies have shown that apomorphine-induced stereotyped behaviour can be conditioned: after repeated pairings of defined stimuli with the drug effect, the presentation of the external stimuli alone elicited stereotype sniffing, licking, and gnawing. Since apomorphine, an agonist at dopamine receptors, also produces a characteristic EEG pattern with an increase of power in the alpha-1 band, the possibility that this effect could also be conditioned was studied. In fact, conditioning with a dose of 0.5 mg/kg apomorphine (s.c.) led to a significant increase in the number of short-lasting episodes with enhancement of the power in the alpha-1 range in the presence of the conditioned stimuli, according to a comparison of the results obtained in the conditioned group and those of the controls ("pseudoconditioned"). Moreover, behavioural studies were performed simultaneously in order to find possible correlations between conditioned effects on EEG and conditioned alterations in behaviour. In general, a fair correlation between the increase of power in the alpha-1 band and stereotyped behaviour was found. This was also the case during extinction, when the conditioned stimuli were repeatedly uncoupled from apomorphine administration: both behavioural parameters and EEG alterations showed similar time-courses and had almost disappeared during the fourth extinction session.

EEG activity after activation of dopamine receptors of D-1 and/or D-2 type was studied by using telemetric recordings in rats. Apomorphine, a preferential D-2 agonist, produced a characteristic increase in the power of alpha-1 band (7.00–9.50 Hz) when given in doses mediating stereotypies (0.2 or 0.5 mg/kg s. c.). Low doses produced a general increase in the power of all of the bands except beta-2. In particular, delta activity was enhanced which seems to be in correspondence with the sedation observed after these doses (0.02 and 0.05 mg/kg). Haloperidol in a dose which is assumed to block both D-1 and D-2 receptors (0.1 mg/kg i. p.) completely antagonized the alpha-1 activation produced by apomorphine (0.5 mg/kg). A similar, although not complete inhibition of alpha-I activation was found after administration of a large dose of the selective D-1 antagonist SCH 23390 (0.2 mg/kg i. p.). The selective agonist at D-2 receptors quinpirole (1.0 mg/kg s. c.) produced a less pronounced activation of the power in the alpha-1 band than apomorphine.